Vitamin D: Cholecalciferol supplements are the most effective, especially in women.

Vitamin D in women: are colecalciferol-based supplements the best?

The positive effects of vitamin D supplements depend on several factors, such as the form of the vitamin and the timing of administration, but also on gender, genetics, and, to a lesser extent, the body mass index of those who take them. According to recent research, women absorb the vitamin more effectively than men, and supplements in the D3 form are more effective than those of vitamin D2, especially if taken every 2 weeks.

These are the results of a study published in the journal BMC Endocrine Disorders by researchers from the King Faisal Specialist Hospital and Research Center in Riyadh (Saudi Arabia).

The two most important forms of vitamin D: colecalciferol and ergocalciferol

The term vitamin D refers to two precursors with similar biological activity: D3, also known as colecalciferol, and D2 known as ergocalciferol. Both D3 and D2 are inactive but are converted in the liver and kidneys into 25(OH)D, the storage form of the vitamin, and into 1,25(OH)2D, the active form. The blood measurement of 25(OH)D is the most accurate method to estimate the vitamin’s reserve status in the body. Vitamin D is essential for the metabolism of magnesium and phosphates, stimulating and promoting calcium absorption and bone mineralization. 

Its deficiency in children causes numerous adverse effects, such as growth delay and rickets. Adults with severe vitamin D deficiency experience bone fragility (osteomalacia), muscle weakness, and bone pain. These symptoms are commonly found in elderly patients following vitamin D-poor diets, subjects with liver or kidney diseases, reduced vitamin D absorption, or insufficient sun exposure. Beyond bone health, it is now established that adequate vitamin D levels may also reduce the risk of autoimmune diseases, infections, and type 2 diabetes. Only a few animal-derived foods contain significant amounts of vitamin D. 

In particular, cod liver oil, certain fish such as salmon and herring, liver, eggs, butter, and full-fat cheeses. Besides obtaining vitamin D from food, the human body can produce it through a series of reactions triggered by sunlight on the skin. Therefore, in some countries, especially during winter months, vitamin D deficiency is very common; in these cases, dietary supplements can help increase its intake. Both vitamin D2 and vitamin D3 are available as supplements for all age groups. 

The efficacy of vitamin D2 compared to D3 remains a topic of debate, although both forms are considered effective in preventing and treating diseases caused by vitamin D deficiency, ensuring adequate levels of 25(OH)D.

Is form D3 more efficient than D2?

The purpose of the new study was precisely to shed light on the differences between the vitamin D variants, revealing how the effects of D2 and D3 supplements on 25(OH)D blood levels depend on factors such as dosage, treatment duration, and sex. 

Specifically, the study revealed that although all types of supplementation increased blood 25(OH)D levels, this metabolite was higher in subjects who received vitamin D3 compared to those who consumed the D2 form, and among the former, the highest 25(OH)D concentration was found in those who took supplements every two weeks. Furthermore, vitamin D3 absorption was higher in women than men: women showed a 22% higher absorption rate compared to men, and a 49% greater bioavailability. 

These differences seemed due to a higher presence of vitamin D-binding proteins in women, especially those taking oral contraceptives or undergoing hormone therapy in postmenopause, suggesting a relation to female hormones. According to the same researchers, differences between men and women could be related to vitamin absorption, but also to the level of vitamin D-binding proteins, a faster vitamin metabolism, and probably a higher body fat percentage.

Body mass index (BMI) was also a significant factor for D2 levels, but not for D3, and only during the first four weeks of treatment. The link between BMI and supplementation response remains unclear. During data collection, it emerged that subjects with specific genetic variants showed smaller increases in 25(OH)D, suggesting that in some individuals, low amounts of this molecule were due to genetic factors rather than diet or lifestyle. 

The study also showed that participants who received only D2 experienced decreases in D3 levels, as demonstrated in previous studies. According to the researchers, the underlying mechanism of this phenomenon is not due to D2 supplementation but is simply a response to increased 25(OH)D levels.

Study details

The study enrolled 269 subjects aged between 18 and 60 years (41% male and 59% female), who were not taking vitamin D supplements, consumed more than one serving of milk per day, or were exposed to the sun for at least 10 hours per week. Researchers divided participants into groups following different supplementation protocols: some subjects received daily supplements of vitamin D2 or vitamin D3, others a combination of both forms. 

Other groups followed supplementation of D2 or D3 every two weeks, others every four weeks. One group also received a daily placebo. All participants, except those in the placebo group, took a total vitamin D dose of 250,000 IU by the end of treatment with doses ranging from 2,000 IU daily to 50,000 IU every four weeks. 

Researchers collected and analyzed blood samples from each participant before treatment, after the first four days, after seven days, and every two weeks, measuring 25(OH)D levels.

More efficient supplementation for women

According to the researchers, the effects of vitamin D2 and D3 supplements on 25(OH)D levels depend on different factors. In particular, supplements were more efficient in women than men, and vitamin D3 supplements increased 25(OH)D levels more than those containing D2; the latter acted more when administered daily, unlike D3, which was more effective when given every two weeks.

D3 Drops: Omegor's supplement

D3 Drops is a dietary supplement providing 400 IU of colecalciferol (vitamin D3) per drop. The Omega 3 supplement, produced by Omegor, can be used in all cases of increased need or reduced dietary intake of vitamin D. 

Source: Hammami, M.M.; Yusuf, A. “Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial”. BMC Endocrine Disorders.