Optimize Iron Levels and Improve Cardiovascular Function

It’s important to know where your iron level is and which direction it might be moving. In fact, when it comes to assessing cardiovascular health, its far more important than measuring cholesterol and most other lipids. The relationship between blood iron levels and cardiovascular disease has a classic U-shaped curve. Both low and excessive amounts of circulating iron cause increases in heart failure, myocardial infarctions, as well as diabetes and all-cause mortality. Even within the “normal” range there is a significant rise in risk as iron levels move away from the low-mid to mid range values for most test measurements.

Essential for so many critical processes and reactions in the body, iron has always been prioritized as a marker to measure. It’s the first nutrient to screen for in populations with suspected deficiencies. Every routine blood draw as part of an annual physical will include at least two tests that attempt to capture functional levels. These efforts are for good reasons. The prevalence of anemia is high in many demographics. The insidious nature of an iron deficiency is often underestimated. Almost every aspect of life is impacted. At first subtle, maybe a little less energy. Gradually immune function and cognitive skills start to decline. Most notably, anemia impairs a child’s ability to grow and learn. It deserves all the attention it gets from medicine. Of course the emphasis has always been placed on ensuring adequacy. As with so many public health issues, it’s triage. Many processed foods for instance, have some level of fortification. These efforts started back in the 1930’s and have helped millions of people have a better quality of health. Along the way however, less attention has been paid to those at the other end of the iron-related spectrum: those who absorb and store it efficiently.

For most people iron is difficult to absorb. The most bioavailable type of iron is known as heme iron. Sources are meat, fish, and shellfish. Not all animal proteins offer the same help. Dairy foods and eggs actually inhibit the iron absorption from other foods that might otherwise be good sources. Dairy products can be rich in calcium and egg yolks contain the protein phosvitin, the richest source of phosphorous in nature. Both have a high affinity for iron and bind it quickly, forming non-absorbable complexes. One hardboiled egg yolk for instance, will reduce iron absorption by 30% at any given meal. Non-heme iron, the type that is found in plants, is poorly absorbed under ideal conditions. Some combinations can help overcome this. Adding an acid for instance, especially ascorbic acid (vitamin C), to a meal that contains this type of plant-based iron can improve its absorption. But it’s an uphill battle as there are far more components to whole plant foods that work against the process overall. Fiber, phytic acid, and tannins as some of the best examples. Equally important to understanding the challenges of absorption is the fact that the body is not good at eliminating excesses. Without blood loss, levels rise significantly as we get older. And excess iron is harmful to the body’s tissues.

While there are multiple ways to measure an individual’s iron levels, each has limitations. Some, such as serum iron, are very short term representations. This test result would fluctuate greatly from one meal to the next. Hemoglobin and hematocrit levels are mid-range, red blood cell-based measures. These provide a measure of available iron over the life span of those red blood cells, about 3-4 months. Ferritin however, is the best at reflecting long-term iron reserves. Each ferritin molecule can hold somewhere between 4000 and 5000 iron atoms, releasing it slowly on an as-needed basis. Because it can drive oxidative stress, iron needs to circulate in a stored but readily available, more stable, less reactive version. Ferritin accomplishes all of this to a large extent. It’s the first place where deficiencies appear and it’s also where the first signs of excessive iron accumulation show up. Both are a major problem for heart muscle and artery walls.

With an iron deficiency, heart muscle has poor myocardial oxygen use and will struggle to generate enough energy. Overtime that cardiac tissue weakens and heart function deteriorates to failure. Higher than optimal levels of iron will oxidize LDL molecules generating the only true pathogenic version of cholesterol. Maybe worse, even moderately elevated iron levels have been shown to degrade nitric oxide so rapidly that it can’t support blood vessel dilation and normal artery wall function.

What are considered normal ranges for many of these iron markers and the optimal physiological range are very different. It’s difficult to explain given the amount of research that would bring some of the lower and upper ranges into question. In the case of hemoglobin the differences exist but they are less dramatic than with other measures. A typical normal range for hemoglobin is 14-17.5 g/dL for men and 12-16 g/dL for women. However 14-16 g/dL for men and 13-15g/dL for women are associated with less heart-related issues. It’s important to remember that hemoglobin is a more short term representation of available iron. The differences between the normal ranges and optimal values for hematocrit and serum ferritin are far more dramatic.

Here are the normal ranges for both and what we should aim for:

Standard Reference Range Optimal

Hematocrit Women 36-48% 36-44%

Men 39-54% 40-45%

Serum Ferritin Women 15-300 ng/mL 45-100 ng/mL

Men 30-300 ng/mL 60-120 ng/mL

Typically, low to low-normal ferritin levels produce at least some symptoms. Rapidly thinning hair, an inability to adapt to or warm up in a cool room, fatigue, not adjusting or catching one’s breath with moderate aerobic exercise, and brain fog are all signs that there’s just not enough iron for everything the body is trying to do. Unfortunately there’s no signs or common indications of high levels of iron. Only in extreme iron-overload cases, such as hemochromatosis, are there clues that damage is occurring. In adults between the ages of 45 and 65 for example, a hematocrit level of 45% compared to 42% is associated with a 4X risk of diabetes and even greater increased risk of suffering an MI or heart attack in a 10 year follow up period. For the same age range with serum ferritin, research suggests that every 10 ng/mL rise from the high end of the optimal range (100 ng/mL for women and 120 ng/mL for men) results in a corresponding 10% increased risk of developing coronary artery disease in a 5 year follow up period. By the time a serum ferritin level hits 200 ng/mL for a 45 year old adult, two things have happened: their risk of having a heart attack is up at least 80% and they will have more inflammation. Levels that hit 200 ng/mL (well within the normal range) are often indicative of infection as well. Overall, these are huge increases in risk that make all of the standard cardiovascular disease risk measures (cholesterol, LDL, ApoB, etc) look trivial in comparison.

If an individual discovers that their hemoglobin or hematocrit are outside of the normal range, it is safe to assume that their serum ferritin is as well. It’s still important to have your physician order the test so that you a baseline value to compare to after a few months of making some adjustments. That serum ferritin value is going to be the best indicator of long-term iron status and it’s where the need to make changes will show up first. Here’s how you can manage your iron levels and get into the optimal range.