Vitamin D as a substance in food.

Vitamin D according to current law, can be used in food
in 2 permitted forms: ergocalciferol (D₂) and cholecalciferol (D₃). Ergocalciferol is a substance characteristic of the plant and fungal world. The most popular commercially available source of cholecalciferol in the input raw material for the production of vitamin D preparations₃ is sheep lanolin. However, it is not a raw material suitable for vegans. However, there is an option to obtain cholecalciferol from seaweed - such a raw material is vegan and more expensive. Vegetarians and vegans are particularly at risk of vitamin D deficiency, as the natural sources of cholecalciferol in food are primarily fatty fish and dairy products. Vitamin D is a vitamin that the human body can biosynthesize in the skin, but it is influenced by many factors, including: time of year and day, cloudiness and air pollution, latitude, use of filter creams, body surface exposed to the sun, pigmentation and skin aging. Skin production of vitamin D is often not sufficient to meet the daily requirement most days of the year, especially for our latitudes.

Both of these forms: ergocalciferol and cholecalciferol - are non-hydrolyzed forms with decent absorption. They are biologically inactive and require transformation in the body into an active form. Hydrolyzed forms of calcitriol: 25 (OH) D show several times higher absorption, however, they are not allowed for food enrichment in the EU (these are medicinal substances). However, it is worth mentioning here that in 2021 EFSA (European Food Safety Authority) issued a positive safety opinion for calcidiol monohydrate. Perhaps in the future, a third permitted form of vitamin D will appear for the first time in hydrolyzed form as a new food ⁽¹⁾.

The process of absorption in the body.

Vitamin D belongs to the group of fat-soluble vitamins - it is built on a steroid skeleton, so it is a lipophilic substance. The process of digesting vitamin D takes place partially already in the stomach (gastric lipases and acids pre-emulsify and prepare the fatty matrix for subsequent steps). Hence, it can be assumed that the use of the enteric envelope of the preparation together with vitamin D can negatively affect its absorption.

Then the absorption process takes place in the small intestine in its proximal part (duodenum) and jejunum. It does not seem reasonable to use the extended-release form, due to the need for emulsification, which takes place mainly on the initial section of the small intestine. It consists mainly of absorption through the formation of chylomicrons. In short, enzymes (bile acids) pre-emulsify the fatty matrix, then micelles (chylomicrons - liposomes) are formed which serve as a lipoprotein transporting lipophilic substances (including cholesterol, triglycerides) from the small intestine to the blood (which is an aqueous environment) and further to the muscles. The second type of transport is via protein channels. Hence the predominance of liposomal forms, in which the vitamins are already enclosed in the transport micelle and can be efficiently absorbed without prior “treatment”. With poor liver function (i.e., poor secretion of digestive enzymes, removed gallbladder), there will be poor absorption of vitamin D from the fat matrix (there will be no emulsification stage). Some studies show,
that in patients with dysfunction of the liver or pancreas, powder preparations (tablets, sachets) of vitamin D are better absorbed.
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For healthy people, in the situation of consuming preparations with vitamin D not With a meal, there will be no stimulation of the liver to secrete enzymes — analogous to taking vitamin D with a fat-free meal, there will be no simulation of the liver to secrete enzymes that digest fats, and there will be weaker absorption. All drugs that affect the absorption of fats will have a negative effect on the absorption of fat-soluble vitamins. It is believed that the form of cholecalciferol (D₃) is better absorbed than ergocalciferol (D₂), but the data is ambiguous. Both forms are absorbed slightly by other channels.
Connection D₃ with D₂ in one capsule could make sense, because it would exhaust all potential transport routes from the intestine to the blood ⁽²⁾.
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Stability in preparations

Cholecalciferol and ergocalciferol are lipophilic (fatty) substances. The higher the lipophilicity of the carrier, the better absorption occurs. This is an important physicochemical parameter affecting biological activity. The pharmacological action of a significant amount of substances correlates with their lipophilicity and allows to predict absorption, distribution, metabolism and excretion, that is, the behavior of substances in the body. Vitamin D in a soft capsule on a fat carrier will have the best absorbability. Tablets, powders (with lactose), ethanol solutions, and finally aqueous solutions perform worse.

The more fatty carrier, the better the absorption of vitamin D3.

pH affects the stability of vitamin D. In an acidic environment (below 4), it is unstable. Pure fresh oils have a slightly alkaline pH, over time sensitive oils (polyunsaturated, drying) can become rancid - this causes a decrease in pH and degradation of the vitamin. That is why it is so important to work on quality oils. Soft capsules, thanks to the tight seam, provide an ideal environment for the stability of the oil and the vitamins dissolved in it. Making such capsules is possible only on top-class automatic capping machines and with many years of experience of the operators working with them.
The stability is slightly worse in the preparations with drops, where each dosage of the preparation causes movements of the oil as well as the air inside, creating conditions for the oxidation of the preparation. The addition of antioxidants (tocopherols, BHT) and higher technological surpluses compensate for these losses.

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In our plant we have a modern blister line and high-quality PVC/PVDC films, with a minimum OTR (Oxygen transmission rate), thanks to which the packaged preparations meet the dose criterion throughout the shelf life. It is also worth adding that not only the thickness and type of PVC film is important, but also the design and shape of the blister slot.

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Light (UV) causes the degradation of vitamin D. In order to eliminate this effect, it is possible to dye the entire shell or only one half of it for an interesting aesthetic effect (commonly used dyes are: cocoa, natural caramel, yellows). White or orange PVC/PVDC film can be used. Usually, however, the use of an appropriate supplement, as well as packaging in a carton/bottle protecting from light, is sufficient to eliminate the effect of UV rays on vitamin D. Iron oxides from the shell can migrate, and the presence of metals (Cu, Fe) causes degradation of vitamin D. Antioxidants or chelates (EDTA) are used to counteract this effect. It therefore seems critical to determine the level of these metals in the carrier (oil) and to use oils as purified as possible.

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The most popular and compatible carrier for fat-soluble vitamins is MCT. Short and medium chain fatty acids are very well absorbed and are quite stable in storage. Vegetable refined oils are more resistant to oxidation than cold-pressed (unrefined) oils ⁽³⁾.

Dose, dose and once again systematicity.

The recommended daily intake for adults is only 5 µg, or 200 IU! The WHO already recommends the use of 2,000 IU of vitamin D. The maximum doses for vitamin D in Poland are 2,000 IU (50 µg) for dietary supplements intended for the healthy population of adults up to the age of 75 and 4,000 IU (100 µg) for dietary supplements intended exclusively for healthy people over 75 years of age (vitamin D absorption decreases with age). The EFSA Scientific Panel has established a maximum tolerable intake level of 100 µg per day for adults. Vitamin D is very difficult to overdose, it is one of the safest vitamins. There are known cases of administration of 20,000 IU — 250,000 IU per day, with no observable adverse effects. Despite this, it is recommended, first of all, to be systematic in the use of preparations with a dose recommended by specialists of 2,000 - 4,000 IU per day. The use of vitamin D in the form of a so-called bolus ensures optimal vitamin D levels only for a few days ^{(4), (5)}.
Raw materials of vitamin D available on the market are in oil and dispersed — powder form. They can be successfully added to every possible pharmaceutical form: tablets, soft capsules, drops, sachets, and the required amount of such raw material is only a few mg to obtain 100% of the recommended dose of vitamin D. Thanks to this, virtually any existing preparation can be easily fortified with vitamin D.

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