This is a study that is best understood in the context of other nutritional-based papers for CV risk. It is a very well-done and robust study. It has a large study sample population and uses a validated food questionnaire with well-described outcomes.
The downside of any study like this is that when researchers set out to study a specific macronutrient or food ingredient such as isoflavones, it is usually not possible to measure it in the context of an observational study. It is really a study about self-reported intake of tofu, soy and those types of products that have isoflavones in them. When the title of the study says “Isoflavone Intake and the Risk of Coronary Heart Disease,” it is really about the intake of foods with isoflavone and the risk of CHD. The researchers acknowledge this in the clinical perspective section of the paper: “Increased intake of isoflavone-rich foods such as tofu” is associated with reducing CVD risk.
To understand this, much like any other nutritional study that is not a randomized trial, you have to understand that you are talking about an association in an observational study, and that it is really an observation of a dietary pattern rather than specific foods, nutrients or macronutrients themselves.
With that caveat, it adds knowledge to what we currently know about food and dietary patterns and risk for heart disease. It goes along with knowledge that we have about the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet that can lower the risk for CVD.
Foods that are rich in isoflavones such as tofu and soy, especially among young women, is associated with lower risk of heart disease. We cannot tell from this study why that is or what is driving that mechanistically. There are different theories out there mostly relating to roles around inflammation and cholesterol handling, but this adds to the body of literature.
Probably the most important takeaway is that it provides guidance for when you have a patient who is trying to think, “What can I do with my dietary patterns to improve my general health,” rather than taking several supplements; it’s more about dietary patterns and a healthy lifestyle. That lifestyle should include eating patterns that we have evidence for like the DASH diet, things that are high in potassium, low in sodium, low-fat dairy, lots of fruits and vegetables and those types of foods. The Mediterranean diet emphasizes olive oil, nuts and legumes. Now foods that have isoflavones in them such as tofu, especially in a plant-based diet, which is something that is becoming very hot nowadays, that can go into doctors discussing dietary healthful patterns for their patients. This was another aspect of the study, and that is the clinical implication that we should take home.
I don’t think it means that we should eat five times the amount of tofu and soy that we had previously been eating. Focusing our diet completely on that is a bad idea, and that is not what these researchers studied. Furthermore, there is some concern about excess soy intake and whether that actually has an adverse relationship with metabolic outcomes.
It is all about moderation and pattern rather than amount anyway. People who tend to eat plant-based diet will tend to eat a healthier-pattern diet in any case.
When I first reviewed this paper, my main criticism was that the researchers are not really looking at isoflavones. They went back and tried to assess isoflavone content within the different foods that they looked at. That was helpful and adds to the validity of the study as well.
Just like any other nutrition observational study, the most robust evidence we can have is from a randomized controlled trial. Trials like PREDIMED and DASH were randomized studies. So far, those have outlasted all of the other diets out there like the fad diets with evidence. If you are going to double down on isoflavones, tofu and soy, a randomized trial is required. It would have to be in a large patient population with long-term follow-up. That may or may not happen.
For nutritional research, if you are going to rely upon small clinical or larger observational studies, then it is really about dietary patterns. If you are going to do randomized trials, you can get to the nitty-gritty of specific additives or food items that can provide further evidence. Other than that, you just have to understand the limitations of nutritional research and why they are difficult to conduct, which is for many reasons. We also have to understand that when we have observational research in nutrition, that may be the best evidence that you do have and that is OK as long as you understand limitations and work within the context of what the data actually say rather than trying to extrapolate to supplements of tofu or isoflavones because that is not what the data are actually showing.
Ian J. Neeland, MD, FAHA
Cardiology Today Next Gen Innovator
Assistant Professor of Medicine
Dedman Family Scholar in Clinical Care
Division of Cardiology, Department of Internal Medicine
UTSouthwestern Medical Center
Disclosures: Neeland reports he is an associate editor of Circulation who reviewed the present manuscript before publication.