The Discovery of Lactoferrin
In 1939, Sorensen and Sorensen discovered a peculiar protein they called lactoferrin when looking at the contents of whey (a milk protein) in bovine milk. They named the protein lactoferrin because it was rich in iron, which gave it a reddish-pink color that has since prompted its nickname “pink gold.” For decades, researchers were unsure of the role lactoferrin plays in the body or its relationship with iron.
It wasn’t until the 1960s that researchers began unraveling the mysteries behind lactoferrin. In 1960, scientists successfully purified lactoferrin from both human and cow milk, which helped pave the way for additional research into the structure and function of the protein. In uncovering lactoferrin’s structure, the researchers found that the protein can bind two iron ions, partly explaining its interaction with iron. The structure of lactoferrin is largely conserved between the versions found in human and bovine milk with some minor differences. Notably, though, the concentration of lactoferrin across different milk types varies. In cow’s milk, lactoferrin is present at a concentration of just 0.5mg/L (less than 1% of the total protein content!). In human milk, however, the concentration is much larger at 1g/L (roughly 15-20% of the total protein content!). Lactoferrin concentration even varies by the stages of milk – with higher levels of lactoferrin present in colostrum, the “first milk” after childbirth, compared to mature milk.
Lactoferrin exists in most other mammalian milk too: from sheep to camel and even goat milk. If you’re wondering how it’s possible that lactoferrin is seemingly everywhere, a recent paper found that the gene duplication that resulted in the precursor to lactoferrin occurred more than 580 million years ago. Given that lactoferrin is found across the animal kingdom and has existed on earth for far longer than the earliest known humans, it must play an important biological role, but what exactly does it do?
What Does Lactoferrin Do to the Body?
Scientists have been investigating the role of lactoferrin for decades, and across the vast literature on the topic, there are three main areas where scientists agree that lactoferrin is hard at work: in supporting iron regulation, gut health, and immune function.
Lactoferrin is a member of the “transferrin” family of proteins, which are known for their ability to bind iron. Lactoferrin has 2 “lobes” to its structure and each lobe can hold one iron ion. This conformation allows lactoferrin to hold onto these iron ions very tightly without letting go, even across various conditions such as changes in pH. Because lactoferrin can exist in iron-bound or non-iron-bound forms, researchers have labeled the different lactoferrin states based on how much iron is bound to the protein. Lactoferrin with very little iron bound to it is called “apo-lactoferrin”. When lactoferrin is fully saturated with iron, it is referred to as “holo-lactoferrin”. In milk, lactoferrin is generally found in an in-between state generally termed “native”: roughly 20% saturated with iron. Because lactoferrin binds to iron, it can play a role in exercise and physical fitness.
Various studies have demonstrated that lactoferrin improves red blood cell production, circulating iron levels, and stored iron levels. Because red blood cells and iron help move oxygen from the lungs to the tissues, these measures are critical for peak athletic performance. By acting on iron levels and red blood cell production, lactoferrin can help you reach your exercise goals.
One study in female athletes found that lactoferrin supplementation curbed lactic acid buildup and fatigue in long-distance runners. The researchers hypothesized that lactoferrin helps the body to better absorb and utilize iron which would contribute to better performance outcomes. So, whether you’re training to beat your marathon time or are just hoping to cross the finish line of your first 5k (we feel you!), consider how lactoferrin may be able to help you reach your goals.
Numerous studies have researched the involvement of lactoferrin in the immune system, but because lactoferrin is such a powerful molecule involved in a diverse array of biological functions, no single study has captured the full spectrum of roles lactoferrin plays in the immune system. What is clear is that lactoferrin’s ability to bind iron contributes to its role in immune function. Iron ions provide strength to pathogens as they try to attack the body. By binding iron to itself, lactoferrin reduces the amount of iron available to these pathogens, weakening them in their ability to wreak havoc on the body. One study found that lactoferrin supplementation provided immune support to healthy male adults by activating cells critical to the immune system. Another study of healthy volunteers showed similar results that suggest lactoferrin aids the body’s immune defense. Not only can lactoferrin boost immune function in the body, but it also contributes to gut health.
Lactoferrin is especially great at maintaining a happy and healthy gut. When consumed, lactoferrin is partially digested by enzymes to produce peptide fragments, while the rest of the protein remains intact in the stomach. It’s been shown that both whole lactoferrin and these peptide fragments have similar biological activities. To aid in gut health, lactoferrin works like a prebiotic to maintain a balanced diversity of intestinal microbiota: the good bacteria that lives in your gut. Lactoferrin can also limit bad bacteria’s ability to set up shop in your gut and multiply. In infants, lactoferrin plays a similar role by helping shape the composition of gut bacteria that develops across the first few years of life. It makes sense then why lactoferrin is so prevalent in mammalian milk. Lactoferrin even helps with digestion and nutrient absorption. This powerful milk protein does this by helping out the epithelial cells that line the gut wall and break down the food passing through.
Lactoferrin is truly a wonder protein that aids the body in more ways than one. Its benefits are only limited by the ability to scale production, something that TurtleTree aims to solve with its upcoming precision fermentation-derived lactoferrin.
How Is Lactoferrin Produced?
A variety of separation and purification methods have been developed to extract lactoferrin from milk. These methods include cation exchange chromatography, membrane absorption, liquid chromatography membrane separation, ion exchange resin, and others. For each of these methods, the recovery rate, percent purity, input materials, and cost of processing vary. Most of these methods use skim milk or whey as the starting material. Some methods have high recovery rates but require difficult procedures, while others are very expensive but make high-purity lactoferrin. Especially as the demand for lactoferrin increases as the benefits of this valuable protein become better understood, more efficient manufacturing techniques will be needed.
Today, lactoferrin remains one of the most costly dairy ingredients available. It can cost anywhere from $600-$2000 USD per kg. While some of this cost is incurred via complicated production processes, significant cost can also be attributed to the sheer amount of starting material needed. With standard processes, 1 million liters of whey is needed to produce between 20-30 kg of lactoferrin. 1 million liters of skim milk produces just 30-60 kg of lactoferrin.
These extremely high costs limit accessibility to this beneficial protein nicknamed “pink gold”. Currently, the majority of available lactoferrin is dedicated to infant formula and food supplements. However, there’s no doubt that given its iron regulation, gut health, and immune support benefits, we could all stand to gain from including lactoferrin in sports drinks, plant-based dairy products, and anything in between!
Producing lactoferrin through precision fermentation could lead the way to greater amounts of lactoferrin available on the market. Because with precision fermentation, the production scale is free from the constraints and climate impacts of animal agriculture – meaning that not only can we produce more lactoferrin, but we can produce it sustainably too. Here at TurtleTree, we’re working hard to deliver precision fermentation-derived lactoferrin that’s equally good for people and the planet.
Sustainable nutrition for all is just around the corner. Reach out to us to find out how you can be a part of this.