Closer look reveals big flaws in mouse study said to link low-carb diets to artery harm; poor study design precludes any inference or conclusion
by Craig Weatherby
In a coincidence that seemed to echo the back-and-forth nature of many findings on nutrition and health, two seemingly contradictory announcements were made on the same day last month.
This latest apparent contradiction concerned the cardiovascular effects of carbohydrates… a term that covers sugars (glucose, sucrose, glucose, etc.) and the chains of linked sugars called starches.
Last month, the American Heart Association (AHA) recommended that people cut back on added sugars, because of the well-establish heart risk of sugary diets.
And on the very same day, the authors of a new study reported that mice placed on a low-carb diet suffered two ill effects:
The apparent, but illusory, contradiction between the AHA announcement and the mouse study has two explanations:
- A significant increase in atherosclerosis—the buildup of arterial plaque that leads to heart attack and stroke.
- A likely loss of ability to repair the kind of routine vascular damage that promotes atherosclerosis if left unaddressed by the body.
Frankly, we were suckered by a misleading press release into mis-reporting the meaning of the mouse study, whose many flaws we dissect below.
- The design of the mouse study was so hilariously flawed that it actually proves little or nothing about the effects of low-carb diets on mouse arteries, much less human arteries.
- Diets that are either extremely high in added sugars or extremely low in carbohydrates (sugars and starches) fall well outside the range of diets the human body became adapted to over many millennia.
While neither extreme is likely to be ideal for arteries or overall health, the available evidence leans much more heavily in favor of low-carb diets than the typical American's high-carb diet.
How America’s sugary diets harm cardiovascular health
Sugars are harmful in excess, especially when they are consumed in the form of empty-calorie snacks and sweets, as opposed to whole fruits rich in healthful fibers, vitamins, minerals, and antioxidants.
Too often, low-carb diets make little distinction between added sugars and carbs from healthful whole grains, fruits and vegetables.
The refined, rapidly digested starches in white flour and other refined rain products from which the fiber and nutrients have been stripped are just as bad as sugars when it comes to promoting diabetes and heart disease.
(It’s important to note that the “resistant” starches found in all beans and in pasta or whole corn that’s been cooked and rapidly cooled
—help stabilize blood sugar levels, and are considered actively healthful.)
The AHA’s new scientific statement is targeted at “sugars and syrups added to foods during processing or preparation and sugars and syrups added at the table.”
And as noted in an AHA press release, “High intake of added sugars, as opposed to naturally occurring sugars, is implicated in the rise in obesity. It’s also associated with increased risks for high blood pressure, high triglyceride levels, other risk factors for heart disease and stroke, and inflammation (a marker for heart disease).”
(They should have included refined starches such as white flour in their advice, since there’s little distinction between such starches and added sugars in terms of their effects in the body.)
The AHA statement says that women should consume no more than about six teaspoons of added sugar a day for and men should eat less than nine teaspoons daily.
To us, that still sounds like a lot of added sugar, but a report from the 2001–04 National Health and Nutrition Examination Survey (NHANES) showed that the average American’s intake of added sugars totaled a whopping 22 teaspoons per day ,or two to four times as much as the maximum recommended by the AHA.
Sugar-sweetened drinks are the leading source of added sugars in Americans’ diet, with one 12-ounce can of regular soda averaging about 130 calories, derived from about eight teaspoons of corn syrup or cane sugar.
So far, so good. In fact, many researchers would say it’s high time the AHA took a stance against excess sugar, which has long been linked, separately, to increased risk of diabetes and cardiovascular disease. And of course, diabetes often leads to cardiovascular disease.
Given the charge against excess sugars, what are we to make of new animal study that finds low-carb diets actually harm their artery health?
People should make very little of the results of this ridiculously flawed study.
Unfortunately, we trusted the highly misleading press release from Boston’s Beth Israel Deaconess Medical Center (BIDMC) when we first reported this news (We've edited this article to correct the misimpressions we conveyed).
Now that we've read the full journal article and had a chance to dig deeper, it's apparent that the researchers at BIDMC are guilty of distorting both the facts and their meaning.
Many commentators have since accused the researchers of deliberately trying to demonize popular low-carb diets. Instead, we think they were just being lazy and sloppy... flaws found in all too many scientific studies.
Seriously flawed mouse study raises unwarranted alarms about low-carb diets
Writing in the current edition of the Proceedings of the National Academy of Sciences, a scientific team at Boston’s Beth Israel Deaconess Medical Center (BIDMC) reported that mice placed on a very low-carbohydrate/high-fat/protein diet for three months showed a significant increase in atherosclerosis… and an impaired ability to form new blood vessels in tissues deprived of blood flow, as might occur during a heart attack (Foo SY et al. 2009).
The study’s co-author Shi Yin Foo, M.D., Ph.D., embarked on the study after seeing heart-attack patients who were on these diets.
Dr. Foo works in the lab named after the study’s senior author Anthony Rosenzweig, M.D., Professor of Medicine at Harvard Medical School… himself an adherent to a low-carbohydrate diet regimen.
Rosenzweig asked Foo to do the mouse experiment, so that, as he said in a press release, “...we could know what happens in the blood vessels and so that I could eat in peace” (BIDMC 2009).
Mice bred to be vulnerable to arterial plaque buildup were fed one of three diets:
In order to keep the calorie count the same in all three diets, they substituted fat and protein for carbs in the two low-carb diets, because that is what people typically do when they are on these diets.
- Standard diet of mouse “chow” (65 percent carbohydrate; 15 percent fat; 20 percent protein);
- “Western diet” (43 percent carbohydrate; 42 percent fat; 15 percent protein);
- Low-carb/high-protein diet (12 percent carbohydrate; 43 percent fat; 45 percent protein).
However, the study design was doomed to produce irrelevant results, for two reasons:
The scientists observed the mice after six weeks, and again at 12 weeks.
- Both of the two low-carb diets were much lower in carbs and much higher in fat and protein, compared with the diets followed by most people who adhere to low-carb plans such as those proposed in the bestselling Atkins, Zone, Perricone, and South Beach diet books.
- They used animals bred to possess an otherwise rare genetic defect in the ApoE cholesterol-processing gene ... and that alone invalidates the outcome.
The mice fed the low-carb diet (#3, above) gained 28 percent less weight than the mice fed the Western diet, but their blood vessels showed a significantly greater degree of atherosclerosis, as measured by plaque accumulation: 15.3 percent accumulation in the low-carb diet group, compared with only 8.8 percent among the Western diet group.
However, these results are mostly meaningless, given the extremely high fat content of the low-carb diet, and the genetically pre-determined disability of the mice to process dietary cholesterol properly.
Wondering why the low-carb-diet mice had such an increase in atherosclerosis, the Boston team measured the usual risk markers thought to contribute to vascular disease, including the animals’ cholesterol and triglyceride levels, oxidative stress (an indirect measure of inflammation and balanced immune function), and blood levels of insulin, glucose and pro-inflammatory messenger proteins.
In each case, despite their genetic inability to process cholesterol properly, there was either no difference in risk-marker measurements compared with the mice on the Western Diet
—which contained the same amount of fat and cholesterol
— or the risk-marker numbers slightly favored the low-carb group.
Since there were no differences in the standard risk markers, none of these results explained why the animals’ blood had more arterial plaque and lacked the ability to form new blood vessels in tissues deprived of blood flow.
However, the authors found an increase in plaque build-up and impaired ability to form new vessels in mice fed few carbohydrates among the mice on the low-carb, high-fat/protein diet after only two weeks.
This impairment was associated with a whopping 40 percent drop in “vascular progenitor cells,” which some researchers think could play a protective role in maintaining vascular health.
While it remains unproven whether these cells help prevent vascular disease, the new findings fit with the idea that injuries to artery walls - such as from homocysteine (a marker for vascular disease) or from oxidized cholesterol - may be counterbalanced by repair work performed by vascular progenitor cells.
While the researchers pinned this outcome on the absence of carbs, they could have easily pinned it on an extreme excess of fat and protein.
Flawed mouse study countered by ample human evidence in favor of moderate low-carb diets
Human studies continue to document the benefits of low-carbohydrate diets, and in the Boston mouse study, harm was seen only after researchers used animals bred to suffer a rare genetic defect in the ApoE cholesterol-processing gene, and fed them diets extremely low in carbs and absurdly high in fat and protein.
The diets the mice received are totally unnatural to mice or humans, yet the press release referred to them as "low-carb", as even though they resembled the moderately low-carb, high-fat/protein diets recommended in the Zone, Perricone, and South Beach diet books.
In fact, the preponderance of research suggests that diets which contain higher percentages of calories from fat and (especially) protein than the standard, carb-heavy American diet may help people from becoming overweight or diabetic.
The authors of the Boston mouse study did not cite the numerous studies showing benefit of low carbohydrate diets compared to the extreme low-fat diet first promoted by Dr. Dean Ornish and subsequently recommended by most doctors to prevent or treat cardiovascular disease.
Intriguingly, standard markers of cardiovascular risk, including blood cholesterol and triglyceride levels, were not changed in the animals fed extreme low-carb, high-fat/protein diets.
Most studies of diet and cardiovascular health rely on such blood markers, and people on moderate lower-carb/higher-fat/protein regimens such as the Zone, Perricone, and South Beach diets have not been shown to suffer worsened blood fat profiles.
(Folks who follow the guidelines of these bestselling books typically lose weight… though not more than people on higher-carb diets with limits on calorie intake. This is because calorie intake, regardless of the source of the calories is by far the greatest determinant of weight gain or loss.)
Our chief objection to promotion of moderately low-carb, high fat/protein diets is that a great deal hinges on the kind of fat being consumed.
In fact, the Perricone, Zone, and South Beach diets arose in reaction to the indiscriminate promotion of high protein intake by the steak-loving Dr. Atkins, who seemed unaware of or indifferent to the major distinctions among kinds and sources of dietary fat.
Unlike fish, for example, red meat is associated with increased rates of cancer, while diets high in the omega-6 fats abundant in cheap vegetable oils (corn, soy, safflower, sunflower) and in processed foods and grain-fed meat and poultry are linked to higher risk or severity of depression, Alzheimer's, arthritis, and other major diseases.
If you're one of the very few people who—like the mice in the Boston study—have a flaw in the ApoE gene needed to process cholesterol, you will need to cut back on dietary cholesterol, and possibly take a prescription drug.
But for most folks, it appears that the best bets for heart and overall health are regular exercise and a balanced, produce-rich diet that's relatively low in sugars, starches, and omega-6 fats and rich in omega-3s.
- American Heart Association (AHA). Association recommends reduced intake of added sugars. August 24, 2009. Accessed at http://americanheart.mediaroom.com/index.php?s=43&item=800
- Beth Israel Deaconess Medical Center (BIDMC). Low-Carb Diets Linked to Atherosclerosis and Impaired Heart Vessel Growth: Study suggests that popular diet regimen may have adverse effect on body's restorative capacity. August 24, 2009. Accessed at http://www.bidmc.org/News/InResearch/2009/August/LowCarbDiets.aspx
- Foo SY, Heller ER, Wykrzykowska J, Sullivan CJ, Manning-Tobin JJ, Moore KJ, Gerszten RE, Rosenzweig A. Vascular effects of a low-carbohydrate high-protein diet. Proc Natl Acad Sci U S A. 2009 Aug 24. [Epub ahead of print]