Vitamin D as a substance in food.

Vitamin D, according to current legislation, can be used in food in two approved forms: ergocalciferol (D₂) and cholecalciferol (D₃). Ergocalciferol is a substance specific to the world of plants and fungi. The most common commercially available source of cholecalciferol used in D₃ products available on the market is sheep lanolin. It must be noted that this raw material is not suitable for vegans. However, there is an option to obtain cholecalciferol from marine algae- such raw material is vegan but more expensive. Vegetarians and vegans are particularly vulnerable to vitamin D deficiency, since 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 this is affected by a number of factors, including: time of year and day, cloud cover and air pollution, latitude, use of sunscreen, body surface area exposed to the sun, pigmentation and skin aging. The skin's production of vitamin D is often not sufficient to meet daily requirements most days of the year, especially for our latitude.

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Both ergocalciferol and cholecalciferol are non-hydrolysed forms with decent absorption. They are biologically inactive and require conversion in the body to an active form. Several times higher absorption is shown by hydrolysed forms of calcitriol: 25(OH)D, but they are not approved for food enrichment in the EU (they 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. So perhaps in the future there will be a third permitted form of vitamin D for the first time in hydrolysed 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 steroidal skeleton, so it is a lipophilic substance. The process of digestion of vitamin D takes place partly already in the stomach (gastric lipases and acids preliminarily emulsify and prepare the fat matrix for the next stages). Hence, it can be assumed that the use of delayed-release capsules in vitamin D products may adversely affect its absorption.

The absorption process then takes place in the small intestine, in its proximal part (duodenum) and the jejunum. It does not seem reasonable to use the delayed-release form, because of the need for emulsification, which takes place mainly in the initial part of the small intestine. It mainly involves absorption through the formation of chylomicrons. In short, enzymes (bile acids) initially emulsify the fat matrix, then micelles (chylomicrons - liposomes) are formed, and serve as a lipoprotein that transports lipophilic substances (including cholesterol, triglycerides) from the small intestine into the blood (which is an aqueous medium) and further into the muscles. The second type of transport takes place through protein channels. This is where the predominance of liposomal forms comes from, in which vitamins are already encapsulated in the transport micelle and can be efficiently absorbed without prior "processing."  With poor liver function (e.g., poor secretion of digestive enzymes, removed gall bladder) there will be poor absorption of vitamin D from the fat matrix (there will be no emulsification step). Some studies show that in patients with liver or pancreatic dysfunction, powder preparations (tablets, sachets) of vitamin D are better absorbed.  For healthy individuals, when taking vitamin D products not with a meal, there will be no stimulation of the liver to secrete enzymes -similarly, when taking vitamin D with a fat-free meal, there will be no stimulation of the liver to secrete fat-digesting enzymes, and weaker absorption of vitamin D will follow. All drugs that affect fat absorption will have a negative effect on the absorption of fat-soluble vitamins. The cholecalciferol form (D₃) is thought to be better absorbed than ergocalciferol (D₂), but the data are inconclusive. Both forms are absorbed through slightly different channels. Combining D₃ with D₂ in a single capsule could make sense, as it would exhaust all potential transport pathways from the gut to the blood⁽²⁾ .

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 effect of a significant number of substances correlates with their lipophilicity and makes it possible to predict absorption, distribution, metabolism and excretion, i.e. the behaviour of substances in the body. Vitamin D in a soft capsule on a lipophilic carrier will have the best absorption. Tablets, powders (with lactose), ethanol solutions, and finally aqueous solutions appear to be worse in the absorption aspect.

The more fatty the 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 oils) can go rancid - this causes a drop in pH and degradation of the vitamin. That's why it's so important to work with high-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. The production of such capsules is possible only using top-quality automatic capsule machines, adding to it many years of experience of the operators controlling the process.
Stability goes slightly down in preparations with drops, where dosing of the preparation causes movement of the oil, as well as the air inside, creating conditions for oxidation of the preparation. The addition of antioxidants (tocopherols, BHT) and higher process allowances compensate for these losses.

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At Europharma Alliance, we typically use a modern blistering line and high-quality PVC/PVDC films with minimal OTR (Oxygen transmission rate), so the packaged preparations meet the dosage criterion throughout their shelf life. It is also worth mentioning that it is not only the thickness and type of PVC film that matters, but also the design and shape of the blister slot.

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Light (UV) causes vitamin D degradation. In order to eliminate this effect, it is possible to use coloring of the whole capsule or only one half of it for an interesting aesthetic effect (common dyes are: cocoa, natural caramel, yellows). White or orange PVC/PVDC film can also be used. Usually, however, the use of an appropriate allowance and also packaging in a light-protective carton/bottle is sufficient to eliminate the effects of UV rays on vitamin D. Iron oxides often used in capsule dying can migrate to the oil, and the presence of metals (Cu, Fe) causes vitamin D degradation. However, antioxidants or chelates (EDTA)
are used to offset this effect. It seems critical, therefore, to determine the levels of these metals in the carrier (oil) and use the most purified oils possible.

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

Dosage, dosage and again - regularity.

The recommended daily intake for adults is only 5 µg, or 200 IU! WHO already recommends a daily intake of 2,000 IU of vitamin D. The maximum in take for vitamin D in Poland are 2,000 IU (50 µg) for dietary supplements intended for the healthy adult population up to the age of 75, and 4,000 IU (100 µg) for dietary supplements intended only for healthy people over 75 (vitamin D absorption decreases with age). EFSA's scientific panel has set the highest tolerable intake level at 100 µg per day for adults. Vitamin D is very difficult to overdose though, and it is one of the safest vitamins. There are well-known cases of administering 20,000 IU - 250,000 IU per day, with no observable side effects. Nevertheless, it is recommended, above all, to be systematic in the use of preparations with the dose of 2,000 - 4,000 IU per day recommended by specialists. The use of vitamin D in a form of the so-called bolus, provides optimal levels of vitamin D only for a few days^{(4), (5)} .
Vitamin D serums are available on the market in oil and dispersed - powder form. They can be successfully added to any possible pharmaceutical form: tablets, soft capsules, drops, sachets, and the required amount of such raw material is only a few mg to get 100% of the recommended dose of vitamin D. This makes it easy to fortify virtually any existing formulation with vitamin D.

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