Crash diets alternating with falling back into old bad habits is a cycle many of us struggle with, but the evidence says slow and steady weight loss leads to better health outcomes. Now, the latest research in Nature magazine pinpoints the molecular mechanisms behind the damage to your heart when you yo-yo. So what is it about cycles of weight loss and weight gain that makes atherosclerosis worse? How does yo-yo dieting up your chances of heart disease?
When it comes to the average person attempting to lose a little extra weight, the data says gradual, consistent lifestyle changes lead to better results, and not just for maintaining a slender physique. Epidemiologists have long known that yo-yo dieting leads to worse outcomes for cardiovascular disease, and now metabolic molecular biologists have discovered that the act of swinging between fasting and free-for-all directly contributes to atherosclerosis or heart disease. What’s more, the research seems to indicate that youthful yo-yo’ing leads to greater risk of cardiovascular disease later in life.
So let’s get that straight. According to scientists, taking a little longer to shed the extra pounds, by exercising or gradually reducing your overall caloric intake, might be easier on your heart and vascular system than bouncing between periods of famine and feast.
Heavy Weight Hearts
How does that work? Isn’t being over weight a risk factor for heart and metabolic disorders? Well, yes, this doesn’t mean that excess low-density lipids/cholesterol in your blood is suddenly safe, but the extremes of going from little food to lots can change how your body deals with accumulating lipids.
New work by a global team of scientists led by researchers based out of Université Paris Cité, France and the University of Cambridge, UK, seems to show that the back and forth between periods of eating a lot of fat and eating very little leads to changes in the behaviour of immune cells that try to clear lipid deposits from your blood vessels.
Wake me up before you yo-yo
Hearing these dire warnings from the doctor should be a wake up call, and it’s tempting to go all out to beat the bulge. Who wouldn’t want to bring their blood lipid numbers down as soon as possible? For many of us, however, it might be better to go the way of the tortoise rather than the hare. Extreme diets are difficult to stick to and are often intended for the short term. Once you stop the diet, it’s all too easy to slip back into old habits and that’s where the danger creeps in.
Drastically cutting back the calories for fast results might seem like a quick and easy solution to unwanted weight gain but when you return to regular food, evidence shows the pounds you lost come back with a little extra. Not only that, but more recently researchers have noticed that yo-yo dieting seems to make cardiometabolic diseases worse. For example studies on people who gain their weight back show increased risks of type 2 diabetes and cardiovascular disease. Worryingly, this risk is not increased in proportion to the new extra weight, it actually seems to accelerate signs of metabolic syndrome.
Not Immune to Change
So why does this matter in terms of yo-yo dieting and heart disease? Two teams of researchers demonstrated in a pair of complementary articles, published last year, that cycling between periods of high-fat diets and fasting changed the way the immune cells dealt with fat deposits in the blood vessels. This makes blood vessel-blocking atherosclerotic plaques form faster and earlier than in consistent over eaters.
In brief, both groups found that white blood cells that should protect and mend blood vessels matured and behaved differently in yo-yo dieting mice.
One team looked at the behaviour of neutrophils. These are the first white blood cells to arrive at the scene when an inflammatory response begins. Neutrophils put out the call that an emergency is going down. While they wait for backup to arrive, they seek and try to destroy potential pathogens. These immune cells act like Sylvester Stallone as Rambo patrolling the back waters of your vasculature, firing off reactive oxygen species at anything that looks suspect. While these cells can do a lot of good being the first at the scene, when they get into the zone, their indiscriminate rampage can cause cellular carnage with friendly fire.
Macrophages, the subject of the second study, turn up later in the inflammatory process. Answering the emergency call from neutrophils, they flood into a site of infection or injury to help remove debris and catch escaped pathogens. Marcophages are probably the most recognizable white blood cells; they are the Pac-Man-like gobbling cells that crawl around eating their way through the mess and helping to repair damaged tissue once the neutrophils have done their job.
Yo-Yo Dieting Gives Neutrophils Trigger Finger
Paris researchers found that mimicking cycles feast and famine by over feeding and then underfeeding young mice repeatedly made them develop atherosclerosis faster than just overfeeding them. The study was carried out over 12 weeks, with the mice being fed similar nutritional content to a typical human high fat western diet or regular mouse food. Despite both sets of mice ending up having similar levels of lipids in their blood, the yo-yo dieting mice developed atherosclerosis sooner, with larger plaques forming in their arteries.
When the researchers looked at the atherosclerotic plaques in the yo-yo mice compared to those in the constant high fat diet, they found that the white blood cells that were trying to to clear the lipids were behaving differently. The yo-yo mice’s white blood cells never seemed to get the chance to settle in at their role taking care of the blood vessels. The dramatic changes in blood lipid levels seemed to keep them in a stage of constant vigilance, unable to adapt. They noticed that similar changes occurred when mice switched from a long-term high fat diet to a yo-yo regime. In both cases the white blood cells were poor at preventing damage to blood cells.
Where Did Your Heart Disease Go?
The yo-yo diet mice’s white blood cells also expressed different genes to those of the continuous diet mice. When the scientists looked up the genes that were more or less active in the you mice’s white blood cells, they found that many of the genes are ones that other scientists had identified as risk factors for human cardiovascular disease.
The researchers now suspect that, just like the mice in their experiment, humans who have certain versions of the genes that encode components of white blood cells are more prone to develop ‘trigger finger’ than others. This means that repeated bouts of crash dieting followed by falling back into old habits are harder on some hearts than others. The take-home message is that long-term gradual reductions in calories in take are less likely to put your immune system on high alert than the maple syrup diet.
Fenland Fat Fanatics
Their competitors at University of Cambridge carried out a similar set of experiments. This time, instead of looking at neutrophils that blast suspect cells with reactive oxygen bombs, the team looked at the Pac-Man like macrophages that crawl around our bodies, gobbling up dead cells, pathogens and debris. Just like the Paris researchers, the fenland scientists put young mice on a yo-yo diet.
One set of mice were put through cycles of high fat feast followed by low-fat famine. As expected, the mice going through cycles of weight gain and weight loss developed atherosclerosis faster than the constant high fat diet group. Examining the macrophages, the researchers found inside the atherosclerotic plaques in their arteries revealed key differences between the yo-yo’ing mice and the consistently fat-fed mice.
The yo-yo mice’s macrophages were having difficultly changing shape to engulf and swallow lumps of fatty deposits on the plaques, dying cells and toxic debris. Zooming in on these differences, the scientists found changes in the genes expressed by the yo-yo mice compared to the full-fat mice. These genes were crucial to macrophage function and were involved in things like the cell’s internal scaffolds that control its shape and ability to move and genes that control how the cell knows which types of geography it’s moving through.
DNA Detectives
This is where the Cambridge group took things a step further than the Parisians. They had identified a small group of key genes involved in macrophage function. Did they have similar effects in humans? The team set to work probing the human genome.
They trawled through studies and databases from genome-wide association studies that hunted for versions of genes that show up in people with atherosclerosis. It turns out that the human versions of the very same genes that were altered in yo-yo dieting mice were strongly associated with cardiovascular disease in humans. This suggests that a similar process could be behind disease progression in humans.
The team proposed that the high levels of fat released into the blood by rapid weight loss confuse the macrophages, preventing them from eating the problem patches of dying tissue and fat deposits in atherosclerotic plaques. If we combine it with the data from the Parisians, we can build the picture a little more.
Slow and Steady Wins The Race
So what might be behind yo-yo dieting’s deleterious effects on our hearts? When we lose weight, we release fats into our blood stream so that our cells can break them down and extract energy from them. Both the fats and the waste products are watched by our immune system to prevent them from causing blockages or poisoning us. When our white blood cells encounter these fats slowly over a long period of time, they gradually clear them. Some cellular changes might take place but as long as the system isn’t over whelmed, the white blood cells are in balance. The problem comes when the fat release isn’t slow and steady but repeated. When fats are released in spurts separated by time, it appears that the white blood cells start undergoing changes.
We don’t have a full picture of exactly what it is about the fats that cause the white blood cells to change, but what we do know is that the mice who yo-yo dieted were more prone to developing heart disease with bigger, nastier atherosclerotic plaques. The mice on continuous high-fat diets also developed atherosclerosis but slower. The answer? Slow and steady beats fast and inconsistent. Genetics are involved- some people carry versions of the genes that are more easily altered than others.
References
Takaoka M, Zhao X, Lim HY, et al. Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis. Nature. 2024;634(8033):457-465. doi:10.1038/s41586-024-07993-x
Lavillegrand JR, Al-Rifai R, Thietart S, et al. Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming. Nature. 2024;634(8033):447-456. doi:10.1038/s41586-024-07693-6