Study on low-carb diet leading to atherosclerosis in mice bad news for rodents, not for humans

Dr. Anthony Rosenzweig says his mice prove low-carb bad for the heart

In September 2009, my brand new book 21 Life Lessons From Livin’ La Vida Low-Carb: How The Healthy Low-Carb Lifestyle Changed Everything I Thought I Knew is slated to be released at long last (YEAH!) and I am excited to be able to share so much of the knowledge I have gleaned from personal research and interviewing experts about diet, health, and life in general over these past five years of living the low-carb life. Looking at Lesson #19 of my book, it says “You can’t always trust or believe the negative studies on low-carb.” How timely because there’s a perfect example of this appearing all across the media today with so-called damning research about how a low-carb diet negatively impacts vascular health. Hoo boy!

In a study entitled “Vascular effects of a low-carbohydrate high-protein diet,” lead researcher Dr. Anthony Rosenzweig, Director of Cardiovascular Research in Beth Israel Deaconess Medical Center’s Cardiovascular Institute and Professor of Medicine at Harvard Medical School, and his research team observed over a 12-week period a mouse model of atherosclerosis (plaque accumulation in the arteries leading to the heart–a precursor for a heart attack or stroke) and fed them one of three isocaloric diets with various fat/protein/carbohydrate ratios:

GROUP 1 — standard mouse “chow” diet (15/20/65)
GROUP 2 — a typical “Western diet” (42/15/43)
GROUP 3 — low-carb, high-protein diet (43/45/12)

Okay, hang on a sec. Before we even get into what Dr. Rosenzweig found in this study, let’s take a look at the diet they are using for this “low-carb” group. While it is indeed low in carbohydrate comprising just 12 percent of the total caloric intake, what’s up with the astronomically high protein content? Most of the reputable low-carb plans out there such as Atkins, Protein Power, and the like are decidedly much higher in FAT (upwards of 70 percent of total calories coming from fat) with only moderate or adequate amounts of protein. A 45 percent protein low-carb diet is nothing at all like what so many of us who are livin’ la vida low-carb would be consuming following a typical low-carb diet.

With that one caveat aside for now, let’s take a closer look at what the researchers did with these mice. They examined them at the six-week and twelve-week mark to see what impact had been made on the various study groups. Weight gain in mice is expected, but GROUP 3 gained 28 percent LESS weight than GROUP 2 — not a surprising result since most scientists acknowledge previous research showing the effectiveness of low-carb diets for weight loss. But when they looked at the blood vessels of the GROUP 3 mice, the researchers found that plaque build-up was nearly double (15.3%) than what GROUP 2 experienced (8.8%). GROUP 1 showed little evidence of atherosclerosis by comparison.

The researchers expressed concern that HUMANS consuming a high-protein, low-carb diet like the one consumed by these mice would lead to an inability to get the proper blood flow to the heart which could result in a cardiovascular event. Interestingly, the study found that the lipid profile of the GROUP 3 mice remained unchanged despite the supposed damage done to the blood vessels. This study was published in the August 24, 2009 online version of Proceedings of the National Academy of Sciences.

What’s my initial reaction to such a study that attempts to put livin’ la vida low-carb in a bad light? I SURE AM GLAD I AIN’T A MOUSE USED IN THIS STUDY! Seriously, are they for real? While mice can certainly be used in certain laboratory experiments to see what would happen to people in similar situations, I am not seeing the connection between a mouse and a human in this “study.” In fact, Nutrition & Metabolism founder and editor Dr. Richard Feinman responded to this discrepancy by noting “the scientifically correct title of this study should be ‘Vascular effects of a low-carbohydrate high-protein diet in ApoE mice’ because that is what it is about.”

Noted Milwaukee, WI-based cardiologist Dr. William Davis added another wrinkle to this study by revealing to Livin’ La Vida Low-Carb that “there are three forms of ApoE mice (2,3,4), each of which responds differently to different diets. For example, apoE2 people (and mice) respond to low-fat diets differently than apoE4 people.” Now this is getting really interesting. So which mice did Dr. Rosenzweig and his team use? It’s anyone’s guess!

Good Calories, Bad Calories author Gary Taubes explained to Livin’ La Vida Low-Carb that this study using mice actually contradicts a great preponderance of the evidence that we’ve already seen in human studies, including how an Atkins low-carb diet improves cholesterol panels, reduces inflammation, lowers blood pressure and more. So why are mice a better model for the development of atherosclerosis in humans than humans? Excellent question, Gary!

Although Dr. Rosenzweig admits it is “very difficult” to know how a diet is truly impacting cardiovascular health even in clinical studies, he insists that using mice fills in the gaps and answers the most pressing questions.

“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,” he stated. “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.”

Okay, let me get this straight to make sure I am understanding you correctly, Dr. Rosenzweig. Are you saying the improvements low-carb dieters in human studies have seen time and time again in their cholesterol, including increases in HDL “good” cholesterol, significant decreases in triglycerides, and an increase in the size of the LDL particles to the large, fluffy, and protective kind, are actually irrelevant as a true indicator of heart health because your mice happened to show negative cardiovascular effects even with all these improved markers? In other words, are we just supposed to chunk all that previous data that shows otherwise and simply believe the mice in your study hold the key to truly understanding what a low-carb nutritional approach is doing in humans? I DON’T THINK SO!

I’m gonna offer up a human case study that demonstrates how low-carb does NOT lead to plaque build-up in the arteries leading to the heart and it in fact does just the opposite.

A 37-year old male who has been eating a high-fat, moderate-protein, low-carb diet for 68 months had a CT scan of his chest conducted last week to see if there were any calcium deposits in the arteries leading to his heart. This heart scan as advocated by Dr. Davis would show any calcification of the plaque that has taken place as a result of his diet and assign a number to indicate the overall risk to cardiovascular problems. When the test results came back from this long-term low-carb eater, they showed his heart scan calcium score was zero. Despite eating a low-carb diet just as these mice did in this study, there was no calcified plaque at all.

By the way, the man featured in this case study is me, Jimmy Moore. WOO HOO!

Dr. Rosenzweig is probably not impressed by my phenomenal heart scan results attributed to low-carb living since he seems to be hedging all of his bets on mice. But the anti-low-carb bias is not just limited to him — another one of the researchers on this study named Dr. Shi Yin Foo, a cardiologist at Rosenzweig’s lab, claims that she wanted to do this study when several of her heart attack patients claimed to be livin’ la vida low-carb. In fact, Dr. Rosenzweig was also eating low-carb at the time which came as a shock to Dr. Foo.

“Over lunch, I’d ask [Dr. Rosenzweig] how he could eat that [low-carb] food and would tell him about the last low-carb patient I’d admitted to the hospital,” Dr. Foo exclaimed. “[Dr. Rosenzweig] would counter by noting that there were no controls for my observations.”

That was one of the reasons why they decided to concoct this mouse experiment “so that we could know what happens in the blood vessels and so that I could eat in peace,” Dr. Rosenzweig said.

Dr. Foo believes the diet composition they came up with most closely matches “a typical low-carb diet.”

“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,” he explained.

Uhhh, no it isn’t, Dr. Foo! Most people who have read a reputable book on low-carb dieting knows that when you remove the carbohydrate you replace it with an increase in the percentage of fat in the diet. Generally it’s not a significant increase in the amount of dietary fat consumed since combined with a reduction in carbs and an adequate amount of protein this way of eating is quite satiating. But knowledgeable low-carbers are abundantly aware of the excessive glucose that comes from eating too much protein (through the process known as gluconeogenesis). And 45 percent of calories from protein is way too much by as much as DOUBLE! I regularly get only about 20-25 percent of my calories from protein and my fat intake is a whole lot higher than 43 percent.

University of Connecticut researcher Dr. Jeff Volek, who has conducted numerous studies on low-carbohydrate diets, told Livin’ La Vida Low-Carb that “no reasonable person would replace carbs with protein to the level these mice consumed.” He added that “mice are horrible models of lipoprotein metabolism and atherosclerosis…because regular mice are resistant to atherosclerosis.”

The researchers expressed shock that all of the typical markers for cardiovascular disease such as cholesterol, triglycerides, oxidative stress, insulin and glucose all came back normal for the low-carb GROUP 3 mice.

“In each case, there was either no difference in measurements compared with the mice on the Western Diet [which contains the same amount of fat and cholesterol] or the numbers slightly favored the low-carb cohort,” Dr. Foo added. “None of these results explained why the animals’ blood had more atherosclerotic blockages and looked so bad.”

Oh, boo hoo, woe is me for ever thinking of going on a low-carb diet! I had no idea things could be so bleak even though all my health markers have been spectacular. Don’t you know this study is being set up purposely to respond to low-carbers who have outstanding cholesterol, triglycerides, blood sugar and insulin levels as if to say, “Sure, your blood works comes back clean, but we REALLY know what is happening to your arteries!” Do they really think we’re that stupid?

Well, for Dr. Rosenzweig, the results of this study were enough to have him cease with his healthy low-carb way of eating.

“Examinations of the animals’ bone marrow and peripheral blood showed that the measures of EPC cells dropped fully 40 percent among the mice on the low-carb diet – after only two weeks,” he remarked. “Although the precise nature and role of these cells is still being worked out – and caution is always warranted in extrapolating from effects in mice to a clinical situation – these results succeeded in getting me off the low-carb diet.”

Dr. Volek notes that a better animal model for conducting a study like this would have been guinea pigs which he says would “have shown low carbohydrate diets decrease cholesterol accumulation and inflammation in the aorta.” And he added that his own research of low-carb diets in humans has shown “in the same 12 week period…that humans consuming low carbohydrate diets have increased vascular function.”

Dr. Davis also chimed in that this study doesn’t jive with what he’s seen.

“I cannot reconcile what this study says with what I see in clinical practice: Low-carb diets yield not only extravagant weight loss, but also marked reductions in triglycerides, small LDL, blood pressure, blood sugar, reversal of pre-diabetic patterns and even diabetes, and is associated with reductions in CT heart scan scores,” he noted.

When Livin’ La Vida Low-Carb asked Kansas low-carb diet practitioner Dr. Mary C. Vernon about this, she quickly concurred with Dr. Davis in her trademark matter-of-fact way of saying things.

“This study just doesn’t fit with what I have seen in patients. I have had patients with pre-existing coronary disease who should have had worsening of their artery blockage have no advancement of their disease when they had repeat cardiac catherization,” she explained. “To have no advancement of disease is unheard of in patient’s treated the standard way in the United States. I have seen patients with high levels of protein leaking from their kidneys return their kidney function to normal. And here is a twist –the diet people are taught to eat after bariatric surgery ends up being a low-carb one. So where is all the accelerated atherosclerosis in those patients?”

What is the take-home message the researchers want to leave with people?

“For now, it appears that a moderate and balanced diet, coupled with regular exercise, is probably best for most people,” they concluded.

Well, how very convenient for you to come to this conclusion! But this little study of yours is absolutely irrelevant because it fails to acknowledge all the previous HUMAN studies that come to the exact OPPOSITE results. If you had a choice between believing a study of mice or a study of humans regarding your heart health, then which one would be more convincing to you? Obviously it’s the human one. And there are plenty of human studies out there that could have been cited by these researchers — but they didn’t do it! As Dr. Feinman explained to Livin’ La Vida Low-Carb, “For them not to cite papers that contradict their findings is dishonest.”

One of my readers shared with me regarding this study the fact that mice are herbivores and, as he put it so succinctly, “may lack the physiological mechanisms to transport and utilize proteins and fatty acids as an energy alternative to glucose”compared with humans. In other words, the diet fed to these mice is very likely unnatural “if the creatures were forced to eat something they cannot metabolize, or metabolize poorly.”

This is something Dr. Vernon expressed concern about as well.

“Someone with more mouse knowledge than I have needs to address the mouse chow composition,” she retorted. “What chow requirements are needed to produce nutritional ketosis in mice? Mice just don’t generally eat this way. How do the researchers know that the change in the mice is from the decrease in carbohydrate? Maybe the mice don’t tolerate the increase in protein in the study diet.”

Dr. Vernon added that it is a great leap of faith to extrapolate human comparisons with these irregular mice diet models — human study participants are necessary to confirm or reject the findings in the animals.

“I would never plan my diet around what makes a mouse healthy — rodents just aren’t very good models for humans. Of course, they reproduce rapidly and they make inexpensive research subjects, so a lot of research is done on mice. But follow-up studies using animals more like humans or humans themselves is needed before conclusions are reached,” she expressed.

My reader went on to give the example of a carnivore like a tiger whose primary diet is fat and protein and imagined what would happen if the animal were to be fed a higher percentage of carbohydrate than normal. Would he be “healthier” than his fellow tigers? Not likely! But isn’t this exactly what the researchers from Beth Israel have done with these mice? It’s a fascinating thing to think about and pokes holes in what is unfortunately being promoted as a reputable study.

Dr. Vernon says she welcomes more research on this, but she will always be more apt to respond to the improvements she has been seeing in her patients over the years.

“I monitor my patients closely, because I know that each individual is unique and may demonstrate a response that I have not seen before. In that case, I would see advancing vascular disease. I haven’t seen it yet, but I will continue to look for it,” she said. “This is why I think doctors need to be involved in nutrition — because this nutritional intervention is as potent as many of the drugs we use and it treats the problem at the source rather than symptom without addressing the cause of the problem.”

Dr. Volek summarized this so-called study in a pithy, yet thorough response.

“Let’s put this paper into context – it used an unsuitable animal model to study the effects of a diet no one would consume and showed results opposite to that seen in a more suitable animal model and humans,” he stated.

Is there anything else left to say after that? Feel free to share your comments below. Or better yet, let Dr. Rosenzweig know what you think about his mouse study by e-mailing him at arosenzw@bidmc.harvard.edu. Releasing research like this and extrapolating human application is irresponsible and unethical if you ask me. Researchers like him should know better!