Formulating for Immunity
Vitamin K: The Underrated Immunity Powerhouse Ready for Product Innovation
Although a number of nutraceuticals help support a healthy immune system, many consumers aren’t aware of vitamin K’s powerful role

Vitamins K1 (phylloquinone) and K2 (menaquinone) are found in many foods and support a host of metabolic immune functions. monticelllo / Getty Images Plus
Immunity is still a powerful trend, and, while probiotics are the major focus of attention extremely important for supporting the body’s immune system, other nutrients, especially micronutrients, have significant roles to play as well. Vitamin K—natural phylloquinone and menadione—is rarely recognized but prominent when discussing nutrition intervention for protecting us from diseases, dysfunction, and the endogenous (think: aging) and exogenous catalysts.
Vitamins and minerals in general are a critical part of one’s diet. Water-soluble vitamins like vitamins B and C are best consumed daily in small amounts because the body does not store them for very long. Fat-soluble vitamins—i.e. A, D, E, and K—are stored in the liver and fatty tissues of the body, allowing for longer availability, but some also carry the risk of toxicity if consumed in excess. Vitamins and their naturally occurring vitamers (different active chemical forms of the vitamin) provide important health benefits, including immune regulation.

K-Marketing
Marketing convenient, tangible health benefits through the enjoyment of vitamin K-fortified products can not only appeal to multiple consumer demographics, but can also lead to improved absorption of vitamin K. If supplements are taken without food, absorption can be sharply reduced, especially with lipid-soluble vitamins, which need a source of fat to be absorbed properly. Vitamin K in a food or beverage product pre-formulated to contain optimal concentrations of vitamin K with the proper fat content improves absorption and is an attractive convenience for all consumers.
Vitamin K has a variety of vitamers, the most common of which are vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Phylloquinone is available from leafy green vegetables, such as kale, spinach, turnip leaves, Brussels sprouts, and broccoli. It is not available from animal products, whereas menaquinone—vitamin K2—is. Vitamin K1 is readily absorbed in the intestine, but only at a rate of around 10-15%. This is because K1 is most often consumed in low-fat food items such as vegetables. However, when accompanied by ingredients containing fat, absorption improves markedly.
Vitamin K2 has somewhat better absorption than K1 because it can be absorbed through the lymph system. It is consumed largely via fat-containing animal or fermented products. Vitamin K2 is also more lipophilic than vitamin K1, thereby facilitating absorption.
It is important to note that all fat-soluble vitamins are critical for homeostasis in the body. Deficiency or excess in one category can lead to reduced efficacy and impaired metabolism of other vitamins and minerals. Prolonged slight deficiency can lead to suppression of various aspects of the immune system, increasing morbidity and even mortality.
Although all fat-soluble vitamins share similar absorption and transportation mechanisms within the body, each individual vitamin and its respective vitamers play a crucial role in maintaining homeostasis of the metabolic and immune processes.
Storage and Function
Vitamins K1 and K2 have very different functions in the body. Vitamin K1 is largely important in the coagulation cascade, where it aids in proper blood clot formation. K2 is more involved in the regulation of bone and cardiovascular health. Vitamin K2 has two compounds of note, menaquinone-4 (MK-4) and menaquinone-7 (MK-7). MK-4 is derived from animal products, whereas MK-7 is largely derived from fermented foods and gut microflora.
MK-4 is found in greater concentration in the pancreas and salivary glands, whereas K1 and MK-7 are found in greater concentrations in the liver. Compared to vitamins A and D, stores of vitamin K are relatively low, which highlights the need for regular consumption of the nutrient. However, the body does have a unique salvage pathway called the “vitamin K epoxide cycle,” which takes place primarily in the liver.
This cycle allows low stores of vitamin K to be recycled indefinitely until excretion, maintaining critical levels of vitamin K in the body when the amount supplied by the diet is insufficient. This is largely why signs of vitamin K deficiency, such as early-stage osteoporosis and hemophilia, can remain unnoticed.
Phylloquinone can be converted to MK-4 through an intermediate compound, menadione (vitamin K3). When metabolized from vitamin K1, menadione converts to MK-4. However, oral supplementation yields menaquinone-9 and -10 residues as opposed to MK-4. Those residues are still biologically active, but have fewer biological roles than MK-4, and high doses of vitamin K3 are toxic. MK-4 has a shorter half-life than the longer chain menaquinones, which means it needs to be consumed more regularly than MK-7 and longer-chain menaquinones.

Role in Immunity
Vitamin K2 is involved in the homeostasis of bone density. Metabolized vitamin K2 derivatives activate osteocalcin and matrix γ-carboxyglutamate (Gla) protein, which are involved in bone density and the coagulation cascade. MK-4 is responsible for apoptosis of osteoclasts, inhibiting bone resorption and reducing pit area. MK-4 also reduces the production of IL-6 and prostaglandins, both of which increase inflammation. Matrix Gla proteins (MGPs) are dependent on vitamin K2 and have a high affinity for binding circulating calcium. They also prevent vascular mineralization while promoting increased bone density.
Secretion of MGPs is upregulated by vitamin D3 bound to vitamin D receptors (VDR) in osteoblasts and osteocytes (bone cells), chondrocytes, vascular smooth muscle cells, and endothelial cells. MGPs are considered one of the most potent natural inhibitors of vascular calcification; they require both vitamin D3 for upregulation of the protein and vitamin K for optimal functionality. Vitamin K2 has an influence on immune responses through a few mechanisms.
In persons with asthma, vitamin K2 reduces the impact of interleukins IL-4, IL-13, and IL-6, reducing inflammation in the lungs and surrounding tissues. COVID-19 patients have similar symptoms, and several studies have reported success in reducing the impact of IL-6 by supplementing with vitamin K.

K Sources
Vitamin K supplementation in food and beverage products is typically limited because most individuals consume enough vitamin K from dietary sources. However, individuals with impaired immune function, cardiovascular diseases, or bone-health issues often require supplementary vitamins, as many metabolic pathways are disrupted, including those of fat-soluble vitamins such as vitamin K. In these individuals, supplementation can be crucial for maintaining health.
While it is recommended that men aged 19 and older should consume ~120mcg/day, women aged 19 and older should consume ~90mcg/day of vitamin K1. Guidelines for vitamin K2 are emerging but are currently between 45-50mcg/day for men and women not to exceed 1,000mcg/day.

An Absorbing Issue
As noted above, the metabolism of vitamin K through the liver is highly regulated; moreover, the liver can excrete excess vitamin K more efficiently than it can other fat-soluble vitamins. This reduces the risk of vitamin K toxicity. However, in individuals with impaired health and/or metabolism, it is fair to assume this regulatory step is not optimal and cannot be relied upon for normal vitamin K metabolism. Therefore, supplementation in food or beverage products may improve vitamin K intake and absorption.
For optimal absorption of vitamin K from a food or beverage product, the product should contain a minimum of 3-5g of fat per serving. In some food or beverage applications, this could potentially impact flavor or texture. Nevertheless, for most formulations, this threshold is so low that there is a minimal chance for off flavors and virtually no impact on food texture. Seasoning or a natural masking ingredient should easily control for even a slight impact vitamin K supplementation could have on a food or beverage.
Healing Factor
Consistent intake of concentrated sources of vitamin K is especially important for individuals on anticoagulant drugs, as vitamin K1 metabolism controls the coagulation cascade. Support with vitamin K1 and K2 through either supplementation or enriched foods and beverages is critical to maintaining a semi-normal coagulation cascade in addition to aiding calcium and phosphorus metabolism for bone health.

Fermentation Factor
Vitamin K2 is a potent functional component of fermented foods and beverages, which are currently extremely popular, especially regarding their connection to gut health—a primary component of the immune system.
Depending on the strain of bacteria used to produce the fermented product, vitamin K2 may not be in high concentrations as a result of the initial fermentation. Increasing the content of vitamin K2 in the fermented product can not only yield increased health benefits but can appeal to a community that is more concerned with its health than any generation thus far.
Gen Z consumers in particular are highly concerned with preventative health, which can be achieved by consuming functional foods or beverages supplemented with compounds such as vitamin K. Moreover, supplemented food and beverage products can also appeal to seniors, as many individuals over the age of 55 experience metabolic dysfunctions and diseases such as diabetes and obesity, which can lead to conditions such as cardiovascular disease or osteoporosis.
Since there are few products currently on the market that boast vitamin K supplementation, it is an area of significant opportunity and open to supporting a range of consumer demographics. The upward trends in functional foods and beverages, especially those targeting immune function, only add to that marketability.
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