Part 36: Essential Micronutrients: Vitamin D3, Vitamin K2, and Antioxidants

This article is an expanded answer to a question raised in the previous one (Article 35). Many wonders whether micro- or macro-nutrients work in the body alone, in combination, or even synergistically. The answer is the latter two, for both types of nutrients. 

Micronutrients:

Key micronutrient supplementation consists of a combination of vitamin D3 (including safe sun exposure guidance), vitamin K2, and antioxidants. Depending on the population or ethnic group and the availability and affordability of a balanced diet, some may need additional nutrients, such as calcium and vitamin A. Most of these and other micronutrients, except vitamin D and perhaps vitamin B12, can be obtained through a balanced diet. Vitamin A, D, E, and K are fat soluble, thus the absorption of these are significantly reduced in the absence of dietary fat.

Each nutrient has its own place in the food cycle, but they also work in conjunction, especially when modulating complex physiological processes, such as bone formation, blood clotting, protein synthesis, tissue generation, reproduction, DNA and cell repair processes, and enzymatic reactions. Let’s look at the three components, vitamin D, vitamin K, and antioxidants separately to understand the basics.

I.     Vitamin D: 

The main function of active vitamin D is to enhance and optimize calcium (and phosphate) metabolism; this includes facilitating intestinal calcium and phosphate absorption, bone mineralization, and calcium conservation in kidneys. The proper functioning of vitamin D requires adequate concentrations of bioavailable magnesium at the site of its active hormone, 1,25(OH)2D (calcitriol) (see Article 34 for more information). 

However, as described previously (Articles 33 to 35), vitamin D has multiple beneficial effects in extraskeletal tissues (pleiotropic effects) that affect all body systems. The enzymes that generate the active hormonal form of vitamin D, calcitriol, and its receptors, are distributed ubiquitously in almost all cells. Vitamin D is essential for procreation, growth, healthy life, and survival. Thus, it is not surprising that its deficiency increases the severity of hundreds of diseases and vulnerability to the development of disorders. 

II.    Different species of Vitamin K:

Vitamin K was discovered in 1929. It is an essential nutrient for blood coagulation (i.e., blood clotting). It is present as two main forms: K1 (phylloquinone) (distributed as Phytonadione; K1) is the predominant form and is abundantly present in most plants, especially, leafy green vegetables, such as kale, spinach, and parsley.

Vitamin K2 (menaquinone) is not abundant and comes primarily from animal (fat) sources, including egg yolk, and fermented foods, such as sauerkraut and natto. Vitamin K2 is thought to have a property that prevents calcification in blood vessel walls, which might reduce the risk of vascular disorders and premature deaths. Vitamin K2 is a bacterial product of K1. 

Vitamin K3 (menadione) is a molecule that occurs in the absence of isoprenyl side chains. In the absence (none) of isoprenyl side chains, the vitamin K2 molecule becomes vitamin K3. It is somewhat toxic, has no known physiological role or place in clinical practice, and thus is not available as a product. 

Vitamins K1 and K2 are required for the γ-glutamyl carboxylation of all vitamin K-dependent proteins. Adequate intake for vitamin K has been proposed to be 90 μg/day for women and 120 μg/day for men.

Different forms of vitamin K2:

Together with vitamin D and calcium, vitamin K2 can be used as an adjunct for the treatment of osteoporosis. Some data suggest that it may also reduce morbidity and mortality in those with cardiovascular disorders by reducing vascular calcification. Meanwhile the vitamin K2 data related to diabetes, cancer, rheumatoid arthritis, and osteoarthritis are promising but not confirmatory.

At least nine variants of vitamin K2 exist; the form is determined by the number of isoprenyl side chains in the K2 molecule. The short-chain product MK-4 is the most common form occurring from fermented foods; it is produced by bacterial conversion of vitamin K1.

In comparison, the longer-chain menaquinones, such as MK-7, MK-8 and MK-9, are more common in certain fermented foods, such as natto, a traditional Japanese food made from soybeans that is fermented with Bacillus subtilis var. natto. Menaquinone-7 (MK-7) is a form of vitamin K2 that has greater bioavailability (and possibly a longer half-life) than does menaquinone (MK-4) after oral administration and may have higher efficacy in vivo. 

MK-10 to MK-13 are produced by anaerobic bacteria in the colon, but they are not well absorbed, and no physiological functions have been attributed to them.

Functionality of Vitamin K:

Is general, vitamin K1 is involved in blood coagulation, and vitamin K2 has roles in skeletal and dental tissues and cardiovascular health. For example, vitamin K1 is needed to generate prothrombin, which is essential for blood clotting (coagulation) and also facilitates the incorporation of calcium into bone tissues. Meanwhile the predominant effects of K2 include bone mineralization and preventing vascular calcification. All three vitamin K molecules likely have other effects currently unknown to us. 

Because of the effect of vitamin K2 on the matrix regulatory protein osteocalcin, the vitamin has an important effect in regulating and improving dentin and dental health, and the integrity of the skeletal tissue. In addition, K2 stimulates osteocalcin, which promote the growth of new dentin, the calcified tissue underneath the enamel tissue in teeth.

However, because of insufficient, no recommendation can be made for taking vitamin K2 supplements for dental health.  Other studies have suggested that higher intake of vitamin K2 could reduce the risks of prostate cancer and improve survival in patients with liver cancer, whereas vitamin K1 had no effect. But more studies are needed before definitive recommendations are made.

Vitamin K—Drug interactions:

It is important to be aware of the interaction between vitamin K and anticoagulants (blood-thinning medications). Those who are taking anticoagulants (blood-thinning medications), such as warfarin (Coumadin), should use caution in taking vitamin K or consuming vegetables, such as spinach and broccoli that contain high concentrations of vitamin K. Because excess vitamin K can make anticoagulants less effective, such can causing disastrous outcomes. Thus, those who are taking anticoagulants should consult the physician who prescribed the medication to seek information about consuming vitamin K-rich foods or prior to taking vitamin K supplements.

Vitamin K deficiency is uncommon. It affects newborns and those with malabsorption issues. These include but not limited to, those who have undergone gastric bypass surgery or have short-bowel syndrome, cystic fibrosis, celiac disease, or ulcerative colitis. In the absence of fat-malabsorption syndromes, most people obtain an adequate amount of vitamin K in their diet. 

Potential synergy: There are some potential positive interactions between vitamin D and K. Some postulate that the combination leads to a synergism that reduces the risk of toxicity, but this remains a matter of controversy. Vitamin K, through its effects on matrix Gla-protein (osteocalcin; also, osteopontin), promotes calcium entry into bone and might prevent vascular calcification (i.e., targeting calcium to bone, rather than to cardiovascular tissue. The following URL provides more information: https://www.vitamindcouncil.org/the-synergistic-relationship-between-vitamin-d-and-vitamin-k/

Essential nutrient supplements: 

Those who are unable to obtain adequate amounts of vitamins D or K for any reason will benefit from supplementation, preferably through diet, including the consumption of foods that are systematically fortified. When targeted to a community (or a country), food fortification programs are highly cost-effective.

Enrichment of food with nutrients adds only approximately 2% to the total cost of food, but the benefits in reduction of incidence of diseases are enormous. The resultant population health benefits are much more important than the extra 2% of the cost. This extra cost can be easily absorbed by the manufacturers of fortified food items or through increased sales of enriched food products.   However, the best option is to obtain the nutrients via an ordinary, affordable, balanced diet.

III.  Antioxidants: 

Antioxidants are compounds derived from food or in vivo that are capable of inhibiting oxidation. Nutrient antioxidants include thiols, vitamin C (ascorbic acid), beta-carotene, vitamin E., etc. There are many plant-derived, natural antioxidants, many of which are polyphenols (phenolic acids, anthocyanins, flavonoids, lignans, and stilbenes), carotenoids (xanthophylls and carotenes), or vitamins (vitamin D, C and E).

Similarly, there are several inherent antioxidant systems within the body that were develop during the evolution, such as glutathione and enzymes (e.g., catalase and superoxide dismutase) that are designed to neutralize excessive oxidative stress.

These antioxidants (some of which are also anticancer agents) are plentiful in all colored leafy vegetables and fruits (especially, berries). In general, the darker the color, the higher the nutrient and antioxidant content. Antioxidants are also present in turmeric and most other spices. However, one need to be careful in consuming marketed products, as a recent report from the FDA confirmed that more than a third of these commercial supplies have dangerous contaminants, including lead and bacteria. 

Antioxidant supplements are rarely needed. Vitamin D also has an independent, potent intracellular antioxidant and anticancer property. Some genetically modified foods are enriched with specific components, including the nutrients mentioned. 

Organic food:

“Organic foods” may not have pesticides or synthetic fertilizer-induced nutrients (nitrogen, phosphorus, and potassium), but they also are not enriched with nutrients (i.e., there is no added nutritional value in organic food). Organically grown crops have less agro-output on a per-hectare basis. In addition, because of recycling of bioaccumulated toxins that are known to be concentrated in plants and compared to synthetic fertilizer, higher volumes of organic fertilizer needed for plant growth, organic fertilizers are likely to supply significantly higher amounts of impurities, including heavy metals, to plants and their vegetable and fruit products.

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Professor Sunil J. Wimalawansa, MD, PhD, MBA, DSc, is a physician-scientist, educator, social entrepreneur, and process consultant. He is a philanthropist with experience in long-term strategic planning, and cost-effective investment and interventions globally for preventing non-communicable diseases [recent charitable work]. The author has no conflicts of interest and received no funding for this work.