CVD, CHO, and Uh-oh: Low-carb Diets and CVD
Abstract & Commentary
By Russell H. Greenfield, MD
Synopsis: In a mouse model of atherosclerosis, researchers showed that a low-carbohydrate, high-protein diet with a macronutrient profile that approximates the maintenance phase of well-known low-carbohydrate diets in humans significantly worsens the development and severity of aortic atherosclerosis in the absence of significant changes in well-established biomarkers for cardiovascular disease. In addition, such a diet appears to impair neovascularization in response to ischemia.
Source: Foo SY, et al. Vascular effects of a low-carbohy-drate high-protein diet. Proc Natl Acad Sci U S A 2009; 106:15418-15423.
Numerous studies have attempted to quantify the cardiovascular effects of a low-carbohydrate, high-protein (LCHP) diet, mainly by focusing on well-agreed upon biomarkers for cardiovascular risk. In this study, researchers went further by directly examining the aortae of animals exposed to a LCHP-type diet for 12-weeks, using a mouse model of atherosclerosis.
Male ApoE(-/-) mice were placed on 1 of 3 diets 1 week after weaning: a LCHP diet (12% carbohydrate, 43% fat, 45% protein, and 0.15% cholesterol), a Western-type diet (WD, 43% carbohydrate, 42% fat, 15% protein, and 0.15% cholesterol), or standard chow (SC, 65% carbohydrate, 15% fat, and 20% protein). Milk fat was the primary source of fat in each of the diets. Sera were examined for markers of cardiovascular risk, and the aortae were examined directly at 6 and 12 weeks for the presence of atherosclerosis. In non-ApoE(-/-), wild-type mice, a hind-limb ischemia model was employed to evaluate perfusion following ischemia.
At 6 weeks, mice on the LCHP diet had significantly more atheroma as a percentage of the aortic luminal area than mice on the WD feed, a difference that was maintained at 12 weeks. Chow-fed mice had minimal amounts of plaque at both 6 and 12 weeks, significantly less than that seen in either LCHP- or WD-fed mice, although the distribution of plaque was similar across all 3 diets (primarily in the aortic arch). The complex plaques identified were similar to those seen in humans.
By trial's end, mice on the LCHP diet had gained less weight than their WD- or SC-diet counterparts. There were no differences between WD- and LCHP-diet mice with respect to total cholesterol levels, both of which were significantly higher than levels seen in the SC-fed mice. Levels of triglycerides, inflammatory cytokines, fasting insulin, and glucose did not differ significantly between WD- and LCHP-fed mice, and mice on either of these diets showed similarly increased levels of oxidized LDL compared with the SC-fed mice. Further evaluation showed that mice on the LCHP diet had markedly reduced (82%-86%) numbers of bone marrow and peripheral blood endothelial progenitors, cells which may be markers of vascular regenerative capacity. In the ischemia/reperfusion model employed, recovery of perfusion was ~39% less in wild-type mice on the LCHP diet compared with those that were WD-fed at 28 days post-surgery.
The authors conclude that in a well-established mouse model of atherosclerosis, a LCHP diet can lead to weight loss compared with SC- or WD-fed mice, but also increases risk of atherosclerotic vascular disease that is not explained by changes in conventional markers of cardiovascular risk.
Commentary
The obesity epidemic has raised the spectre of a pandemic of cardiovascular disease. With more and more people desiring appropriate weight loss, the public has shown a growing interest in LCHP diets. Initially, many health care practitioners doubted that a LCHP diet could offer health benefits, and were then surprised when studies of people on these same diets did not show worsening of results on standard blood tests used to help frame individual cardiovascular risk profiles. And yet, the incidence of cardiovascular disease continues to rise.
LCHP-fed mice gained less weight but developed more severe aortic atherosclerosis and had worsened neovascularization potential in response to tissue ischemia compared with mice fed the SC or WD diets, changes not explained by alterations in serum cholesterol, inflammatory mediators or infiltrates, or oxidative stress. Mice on the LCHP and WD diets were getting essentially the same amounts of fat and cholesterol in their meal.
For years the approach to lessening cardiovascular risk has included appropriate weight loss, and for many the route chosen has been a LCHP-type diet. People often succeeded in losing weight, though many gained it back over time once carbohydrates were brought back into their diets. For those who nonetheless stayed on the LCHP-diet, however, the assumption has been that their cardiovascular risk profile was now improved, and this was often supported by positive changes in their cholesterol levels and other blood tests. It appears this approach is far too simplistic.
It would be extremely difficult to perform a human study directly evaluating the effects of diet on aortic arch atherosclerosis, and the authors of the current study are to be applauded for sound work. True, the data may speak more to mice than people, but this same model has been employed in numerous studies of cardiovascular disease, and the results were found applicable to health and illness in humans. If nothing else, these findings clearly show that the pathophysiology of atherosclerotic vascular disease is still far from completely understood, that our easily determined markers of cardiovascular risk may be woefully inadequate to the task, and that the macronutrient content of one's diet can play a significant role in cardiovascular health beyond that appraised by blood tests alone. Were the changes seen due to increased protein intake? Did they develop as a result of lowered carbohydrate intake? Sadly, this is one instance where the statement "further investigation is needed" could not be more true.
In a mouse model of atherosclerosis, researchers showed that a low-carbohydrate, high-protein diet with a macronutrient profile that approximates the maintenance phase of well-known low-carbohydrate diets in humans significantly worsens the development and severity of aortic atherosclerosis in the absence of significant changes in well-established biomarkers for cardiovascular disease. In addition, such a diet appears to impair neovascularization in response to ischemia.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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