Crystal Engineering


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A new vitamin D ‘made in Spain’ arrives with more advantages.

CIRCE Scientific, a 'startup' created by two friends (from the universities of the Balearic Islands and Barcelona), has developed a crystalline form of this molecule that makes it much more heat stable and prevents dosing errors.

Foto: Unsplash.

By Patricia Matey

30/07/2021 – 05:00

Since the arrival of the SARS-CoV-2 virus, it has undoubtedly been the vitamin that has attracted the most attention from both the scientific community and the general public. We are talking about vitamin D, a hormone whose deficiency has been associated with numerous acute and chronic diseases, both bone and extraosseous. At Alimente we have talked about it on several occasions, both because of its great ‘gifts’ (it strengthens bones, as well as having anti-inflammatory, antioxidant and neuroprotective properties that contribute to the health of the immune system, muscle function and brain cell activity) but also about the fact that deficiency of vitamin D has been associated with an increased severity of covid-19.

In this sense, its possible relationship, even the fact that its deficiency can include a greater risk of contracting covid, has generated so many discussion points, that we have to evaluate the positioning paper of the Spanish Society for Bone and Mineral Metabolism Research (SEIOMM) which recognizes: “Pending the publication of clinical trials that confirm or not its usefulness, the risk/benefit ratio could be favourable to the use of vitamin D (off-label) in the prevention and treatment of COVID-19 in patients with risk, in which it might be reasonable to prevent or treat deficiency, given the known beneficial effect on immunity and respiratory infections.”

Best news from a couple of friends

But the ‘good news’ comes from the hands of two Spanish friends (Fernando Barrera, former director of the Research Result Transfer Office at the University of the Balearic Islands, and Dr Rafel Prohens, researcher at the University of Barcelona and a specialist in crystal engineering), who joined in 2012 under the challenge of developing a more advantageous vitamin D.

Photo: iStock.

It is known that vitamin D degrades easily, especially in heat, humidity, and other types of conditions. In fact, a study published in the ‘Brazilian Journal of Pharmaceutical Science’ quantified the significance of this degradation of vitamins A, E and C in 12 brands of vitamin supplements. According to their analysis, 40% of the samples had lower content of vitamins A and E than declared on the label during the first six months (some even at zero time). At 12 months, significant degradation of vitamins A, E and C was highly significant in approximately 90% of the samples evaluated.


This concept is based on the amount of vitamin in each retail supplement, and that it is the usual strategy to add twice the amount claimed on the label to ensure that, if consumed after one year of storage, despite the degradation suffered, there is still sufficient vitamin D to meet the specifications.
But according to studies carried out by Dr Zane Temona, in her book ‘Vitamin D Deficiency: Causes and Treatment’ (chapter 4): “Even though the use of vitamin D overages is a routine, it poses a serious danger of excessive vitamin D intakes. These can be responsible for toxic effects, mediated mostly through hypercalcaemia.”

“It is common practice to add twice the amount claimed on the label, to ensure that after one year of storage, despite degradation, it contains vitamin D”

Fernando and Rafel set themselves the challenge of improving products with the well-known therapeutic activity of vitamins, by giving them added value through the application of new technologies based on crystal engineering. Currently, Fernando Barrera is the CEO of the company (CIRCE Scientific, the ‘parent’ of the project) and Rafel Prohens, the scientific advisor and director of the research projects, while Joan Perelló is CEO of Sanifit and chairs the Board of Directors of CIRCE Scientific. Joan Albertí and Ignasi Miquel have also joined the team, both with more than 20 years’ experience in the pharmaceutical industry in management tasks of research, development and business management.

The keys

CIRCE Scientific, as its founders highlight to El Confidencial, “is the acronym for Center for the Intelligent Research in Crystal Engineering. Moreover, in Greek mythology, CIRCE Scientific was a woman of great wisdom, a connoisseur of the healing powers of plants and capable of transforming men into animals. According to legend, when she let Ulysses leave her island, she returned him to his human form but renewed and in his best version. Bringing the gap, at CIRCE Scientific, from a deep knowledge of the crystalline state of matter, we combine multidisciplinary scientific approaches that allow us to obtain improved versions of nutraceutical products with known beneficial properties for health. As a metaphor, the founding partners chose the name of the company that best fits this philosophy of development and improvement”.

How vitamins are developed in this way

They emphasise that “many of them, as previously mentioned, are sensitive to heat, humidity, solar radiation, extreme acidity or basicity and oxidising or reducing conditions. For this reason, it is assumed in the food industry that any vitamin product that is developed will degrade to a greater or lesser extent. Thus, vitamin supplements typically use larger than necessary amounts of the vitamin (up to 100% excess) to mitigate this product loss, which leads to production cost overruns as well as generating more waste.

Rafel Prohens

Crystal engineering “is an innovative scientific discipline that is certainly still largely unknown in the field of nutrition. It offers a more effective alternative to overdosing, as it allows the design of new crystalline materials for products of biological interest based on knowledge gained from thousands of crystalline structures of a wide variety of products. The precise combination in a single crystalline species of a nutraceutical principle with another compound acceptable for human use can generate a cocrystal, that is, a new crystalline form with properties superior to those of the starting compound”, recall its developers.

“In the food industry, it is assumed that any vitamin product that is developed will degrade to a greater or lesser extent”.

In the specific case of vitamins, they point out: “We have significantly increased the stability of vitamin D2 and D3 against heat, humidity and light radiation, the main sources of degradation of this important nutrient.

What are the benefits

They insist: “An excess of vitamin (hypervitaminosis) can have effects that are just as harmful to health, if not more so, than a lack of it. This risk is higher with fat-soluble vitamins, since their excess can accumulate in the body’s fat. It is therefore important to be sure of the amount ingested. Today’s diets often do not provide the necessary amounts, hence the expected boom in vitamin supplements.”

But what if we think we are ingesting 2,000 IU of vitamin D3 (as the product label says), but the actual dose is between 1,700 and 4,000 IU? “As we anticipated, based on previous research, manufacturers predict how much each vitamin will degrade from the time the supplement is manufactured until its expiry date, and overdose to compensate for these losses. In this way, they can comply with regulations, which require them to guarantee a content that is at least equal to or higher than what is indicated on the label,” they say.

So, “if you buy a multivitamin supplement that has been produced a month before, and has a two-year expiry date, it is easy to find that it has a content between 150% and 200% of what is indicated on the label,” they add.

Premium Vitamins

The premium vitamins that “CIRCE Scientific has developed, which are expected to reach the market before the end of 2022, will reduce the risk of ingesting excessive amounts and also reduce the risk of suffering from hypervitaminosis. From the point of view of sustainability, the reduction of, for example, 33% of the added vitamin leads to savings in energy, consumption of raw materials and generation of polluting by-products, which in turn implies a substantial reduction in the carbon footprint for each ingested dose of the vitamin,” they remind us.

Market Niche

As the partners explain, “CIRCE Scientific is looking for investment or industrial partners to complete the market launch of its vitamins. To this day, we have already obtained a cocrystal of vitamin D2 and vitamin D3, and we have verified with internal and external experiments the greater stability of our vitamin cocrystal. Now, it only remains to industrialize its production and implement regulatory requirements to start its commercialization. And we continue to investigate other vitamins and nutraceutical products, which we will have developed before the end of the year”.

The future

The icing on the cake comes with knowing that “in the nutraceutical sector there are many products that are very promising, fail to reach their full health benefit potential. Mostly because of their low solubility, stability, or bioavailability. Our goal, based on innovative crystal engineering approaches, can improve any of these parameters. We have already done so with, for example, pterostilbene, a natural product structurally related to resveratrol, but more potent. We have improved its bioavailability 10-fold. We have also improved between 7 to 10 times the solubility of sitosterol and its beneficial effects, such as a greater reduction of cholesterol, decreasing weight gain in obesogenic diet and reduction of fatty liver biomarkers”, they document.

“They are expected to reach the market before the end of 2022. They will make it possible to reduce the risk of ingesting excessive amounts, reducing the probability of hypervitaminosis”

In addition, “we have not only improved the stability of vitamin D, but also that of ubiquinol (better known as coenzyme Q10), which is one of its major drawbacks for its production, logistics and handling. And we have half a dozen other projects in the research phase, with promising results already identified in three of them”.

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