Vitafoods Insights: Shining a spotlight on startup innovation

Vitafoods Insights’ weekly newsletter covers nutraceutical news and analysis all year long, including the best of startup innovation. Here is our pick of three articles showcasing startups making waves thanks to their disruptive ingredients, products, and tech solutions

Female entrepreneurs weary of gendered marketing strategies such as “shrink it and pink it” are taking matters into their own hands

By Kirstin Knight

Femtech innovators are leading the way on personalised, consumer-focused solutions specifically targeting women’s health needs.

Dr Colleen Fogarty Draper is the co-founder and CEO of PhenomX Health, a pioneer in perimenopausal health and nutrition. The startup, which was founded in 2021, is a platform “for women who wish to know more about their personal experience during this life transition and how to treat their health symptoms using nutrition therapies for a healthy and empowered ageing experience”.

It is one of many businesses in a burgeoning category that has experienced incredible growth over the past few years.

Despite the fact that the term was only coined in 2016 – by entrepreneur and Clue CEO Ida Tin –femtech has a market size that is estimated to be worth anywhere from $500 million to $1 billion, according to analysis by McKinsey

However, the same report found that femtech companies currently receive just 3% of all digital health funding.

“The [personalised nutrition] industry is just beginning to realise how important it is to target women, since they are the largest purchasers of personalised nutrition and health for themselves, as well as their families,” said Draper.

She highlighted the work of investor groups such as Goddess Gaia Ventures and Portfolia, which are stepping up to specifically support femtech.

Draper highlighted the historical lack of female-specific research as a major challenge for the sector, citing a 2020 study that found women experienced twice as many adverse reactions to drugs as men.

“Historically… results were analysed by including males and females in the same group and statistically adjusting for their differences to sufficiently normalise the data so that both groups could be included in one larger group to be analysed,” she said. “Higher numbers of people in the same group equated to stronger statistical results.

“Unfortunately, this also equated to serious consequences, such as women experiencing adverse drug reactions nearly twice as often as men. The NIH [US-based National Institutes of Health] now requires sex as a biological variable to be considered in all research. This is an important step in the right direction.”

She pointed to an expanding body of research, including global impact publications “on pregnancy, preconception, lactation, fertility, breast cancer, ovarian cancer, bone health, and even sports nutrition”.

She added: “With more and more digital health products, like the one we are building at PhenomX Health, we are in a position to collect data that help the end user which can concurrently be used to research impact of nutrition interventions on health outcomes.

“This is a less expensive way to conduct clinical studies, which may not replace classic clinic research but can augment and substantiate research to propel the field forward.”

Draper conceded that within the startup community, there have been “improved efforts” to support women’s health entrepreneurs in the femtech arena

She said: “There are new accelerator programmes, such as Tech4Eva, the first femtech accelerator in Switzerland; Station F, Paris’s startup megacampus, [which] initiated a femtech programme last year; and Femtech Lab in the UK, which helps gear up new startups to obtain their first rounds of funding.

“These programmes are helping founders take the early steps they need to build meaningful business enterprises.

“What was different before this? Women’s health startup ideas were often squashed in favour of more masculine solutions. This natural, subconscious bias has occurred as most investors and even startup coaches are male.”

However, she highlighted the fact that femtech companies “are supported by men and women”, adding: “The truth is, the more we collaborative inclusively, the more likely we will be to successfully commercialise meaningful solutions to women’s health challenges.”

What might these meaningful solutions look like?

“I do think brands need to find ways to invest in the research needed to cover the female life cycle,” said Draper. “It would be great to see how programmes could be developed that could incentivise this, since direct-to-consumer brands often lack the funds to invest in the research that is needed.

She added: “In recent years, more and more research has been conducted on the menstrual cycle and nutrition, including athletic performance; and now we see publications in the area of menopause and the Mediterranean diet.

“A recent study of over 100,000 women on menopause symptoms is very encouraging.”

US startup BCD Bioscience is making precision prebiotics through a proprietary process that breaks down polysaccharides into bioactive oligosaccharides with highly targeted health benefits.

By Niamh Michail

BCD Bioscience’s first product is a barley beta-glucan for specific health outcomes – namely improved glycaemic response and the associated cardiometabolic effects.

“We’re trying to actually reinvent prebiotics and instead of going from a standpoint of, ‘We’ve developed a prebiotic. Let’s see what it does,’ we’re [...] going after specific applications and finding the right prebiotic for that application,” said Matt Amicucci PhD, co-founder and vice president of R&D.

The California-headquartered startup has a public partnership with major US pomegranate producer The Wonderful Company, and is exploring oligosaccharides derived from pomegranate pomace, a major sidestream of the juicing industry. It aims to have its first ingredients on the market in 1.5 to two years and is currently in the process of putting together a Generally Recognised as Safe (GRAS) application, with plans to submit a novel food dossier for the EU market.

So, how exactly does BCD Bioscience create precision prebiotics? The company takes natural raw materials – fruit, vegetables, cereals, or agri-food side-streams – and breaks the fibre or polysaccharides into smaller, more bioactive fragments of fibre, called oligosaccharides. It then has a screening process – high-throughput functional assays, bioinformatic tools, and phenotypic screening – that allows it to test how each of these fibres impacts the gut microbiome and the metabolites that the gut microbiome produces.

“[These] are really the bioactives that affect health. So, instead of just having this small palette of two or three different prebiotics to work with, we’ve actually created dozens of new prebiotics that nobody else has been able to get their hands on yet,” Amicucci said.

These prebiotics have targeted health benefits on areas such as immunity, gut inflammation, lowering the glycaemic response to certain foods, and cardiometabolic disease.

BCD Bioscience’s proprietary process does not involve gene-editing, but the startup has some “very unique tools” that allow it to alter the carbohydrate composition of natural products, said the co-founder.

“A lot of the technologies used to look at carbohydrate structure were developed in the 1960s and really not modernised at all,” he said. “So, people are looking at a couple [of] samples a day. We’ve developed methods that allow us to analyse hundreds of samples a day.”

BCD Bioscience stores information about these different samples in its “carbohydrate encyclopaedia”, an inhouse resource that contains the carbohydrate compositions of between 2,500 and 3,000 different natural products. This resource allows it to explore the various features of carbohydrates – the most abundant biomolecule on earth – and look for unique combinations of carbohydrates that look promising.

From there, it extracts the fibres or polysaccharides from the material and applies a Fenton depolymerisation process. This is a non-enzymatic and non-biological chemical process that “chops” the fibres within the raw materials into smaller oligosaccharides – a modification that enhances the fibre’s fermentability by the microbiome.

According to Amicucci, the depolymerisation process is clean, using food-safe iron as a catalyst and then hydrogen peroxide (which later degrades into water) to induce the “chopping” of the polysaccharides into oligosaccharides

The final product is an ingredient that is very user-friendly from a formulation perspective.

“One of the features of the process is that [...] you enhance the ‘formulateability’ – meaning that the [oligosaccharides] are highly soluble and can be formulated like sugar,” said Amicucci. “They don’t have the same sweetness as sugar, but they provide a lot of those binding and bulking [properties] and things like that. But they retain all of those biological properties that make fibre good for you.”

An additional benefit is that these “stealth health” ingredients could allow brands to make fibre-related health claims that were previously unattainable because the required fibre content made the final product unpalatable. While some probiotic brands may wish to add BCD Bioscience’s prebiotics to their products, Amicucci sees bigger opportunities in the bakery and beverage categories.

“Right now, just about any juice or plant-based milk or soda on the market is completely devoid of fibre. And even something you might think has fibre in it – orange juice with the pulp – really has less than one gram per serving. What we can do is [...] take the orange peels that are left over from orange juice processing, apply our process, solubilise all that fibre, and put it back into the orange juice,” he said.

“So, now you have a clean-label juice product that is orange juice with orange fibre. You’re making juice healthier, you’re lowering the glycaemic response to all that sugar in the juice, and [you’re] enabling all of these microbiome-type benefits that are intrinsic to the prebiotic aspects.”

From transgenic plants to cell cultivation and from precision fermentation to high-omega algae, industry disruptors are developing novel methods to produce omega-3 that are fish- and krill-free.

By Niamh Michail

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are long-chain omega-3 polyunsaturated fatty acids that bring numerous proven health benefits for brain function, vision, blood pressure, and heart health, and demand for omega-3 supplements is increasing, with an expected compound annual growth rate (CAGR) of over 8% from 2020 to 2028, according to Grand View Research.

However, levels of over-fishing mean that the oceans’ resources are already stretched. What’s more, 70% of fish oil that is produced is currently used by the aquaculture industry to improve the nutritional quality of fish feed and is therefore not available to meet rising consumer demand for omega-3 oils

In addition to addressing the issue of overfishing, there may another reason to develop alternative sources of omega-3 Rising sea temperatures linked to climate change mean that natural levels of these fatty acids in the oceans may be falling.

The Global Organization for EPA and DHA omega-3 (GOED), which represents the interests of the omega-3 industry, supports the development of novel methods to produce fish- and krill-free omega-3.

“It’s a fact that the total EPA and DHA currently supplied by the oceans cannot meet global demand for even the most conservative recommended daily intake,” said Chris Gearheart, director of growth and engagement at GOED.

“We fully support all companies developing scalable ways to produce EPA and DHA without adversely affecting marine resources, especially as nutritional literacy increases and global demand for omega-3 continues to grow.”

Non-profit organisation the Good Food Institute (GFI), which champions an animal-free food system, echoes this. “There is a need for a more robust supply chain for animal-free omega-3s as ingredients for all three alternative protein production platforms: cultivated, fermentationderived, and plant-based,” it says.

So, what are the next-generation alternatives? How are they being produced, how do they compare nutritionally, and how much potential do they really have to alleviate pressures on wild fish and krill stocks?

UK-based non-profit research centre Rothamsted Research has produced plant-based omega-3 fatty acids by genetically modifying the common commodity crop Camelina sativa to synthesise EPA and DHA. According to the lead scientist behind the research, Professor Johnathan Napier, transgenic plants are a sustainable and environmentally friendly source of omega-3 fish oils for use in novel foods.

Napier and his team of researchers say they have scientifically demonstrated there was no difference in the bioavailability of their EPA- and DHA-rich plant oil in human studies compared with conventionally produced fish oil.

“The only difference [was] that our plant oil is significantly more sustainable!” he said.

Rothamsted Research is collaborating with a US company, Yield10 Bioscience, to commercialise the novel crop. Yield10 Bioscience says its engineered camelina lines produce approximately 20% of EPA and DHA fatty acids, which is similar to the composition of northern hemisphere fish oil.

It has conducted several field tests in the UK, US, and Canada for four years, collecting the oil samples and conducting further studies on both salmon and human consumption. “Equivalence to natural fish oil has been demonstrated,” it says.

While admitting that he was biased, Napier said there were clear benefits of using transgenic crops to produce omega-3 over other approaches

“I am not too familiar with the [cell-cultured] approach, but I can’t imagine that any system that relies on cell culture could compete economically with a plant-based approach. I mean, the cost of growing a plant in a field, versus culturing cells in a sterile environment and using expensive reagents to allow the cells to grow, means that agriculture always comes out on top. This is also true if you compare with systems that are making EPA and DHA via algal fermentation,” he said.

“In addition, whilst it is simple to scale up with a plant-based system – you just plant more fields – if you are trying to scale up with a cell-culture system or fermentation, you need significant infrastructure to support this, plus energy costs, which are obviously increasing dramatically,” Napier added.

Precision fermentation uses microorganisms, such as yeast or bacteria, as a production host to synthesise a specific molecule of interest, and could also be a promising way to produce animal-free omega-3 polyunsaturated fatty acids (PUFA).

The GFI notes that oleaginous yeast, such as Yarrowia lipolytica, may be the most suitable candidate for synthesising fats because it can accumulate large amounts of intracellular lipids.

Scientists have already produced EPA using this method. In 2013, the researchers described how they metabolically engineered the yeast lipid to comprise 56.6% EPA and fewer than 5% saturated fatty acids by weight. “[These] are the highest and the lowest percentages, respectively, among known EPA sources,” they wrote.

However, numerous variations on the idea of producing long-chain omega-3 PUFAs via fermentation may be imagined, according to the GFI.

“Different hosts will pose different advantages and disadvantages. They can be optimised for greater efficiency, and the variety of metabolic pathways through which these compounds can be produced allows a great deal of room for optimisation, both in the interest of cost and scale and in the interest of optimising the fatty acid profile of the final product,” it says.

Cell cultivation, also known as cell culturing, is another method being used to produce animal-derived ingredients without the use of animals. While the technique is mostly being used to develop meat products, it can also be leveraged for omega-3 fatty acids

Spanish startup Cubiq Foods is developing cell-cultured DHA and EPA in addition to a range of cultivated fats for food applications. It has already partially submitted a novel food dossier to the European Food Safety Authority (EFSA) and aims to have a cultivated omega-3 product on the market by 2025.

It uses duck cells in its cell-culturing platform. According to the company’s CEO, Andrés Montefeltro, this is ideal for producing omega-3 in a laboratory because Cubiq wants to produce fats in an animal format, with the right ratio of fatty acids by triglycerides and phospholipids.

“If we produce just fatty acids and then reassemble triglycerides by enzymatic steps, we will produce non-natural fats that probably can be less efficient to become active in the body. Duck cells produce the fat in the proper format, and we don’t need to add steps in order to have the ingredient ready for food development.”

Montefeltro added: “[...] Animals are the perfect production machine for animal fats. Years of evolution bring this capacity. Replacing the animal synthetic pathways by a combination of microbial and chemical steps will be always less efficient for complex molecules. For example, bacteria cannot [make] fatty acids longer than C18. If you push that, by genetic engineering, to C22 and polyunsaturation, you will have a product, but the efficiency will be lower.”

Besides the sustainability argument, another benefit of producing DHA and EPA via cell culturing is the ability to tweak the nutritional format. Cubiq Foods is also working on a second product that uses genetic engineering to achieve even higher levels of DHA and EPA than conventionally sourced omega-3 fatty acids.

Fish and krill do not produce omega-3 themselves; it is present in plankton and builds up in their bodies through bioaccumulation. Using microalgae as a source of omega-3 oils is, in a way, going straight to the source.

The consumer-facing brand Örlo Nutrition, owned by Icelandic supplier Vaxa, uses photobioreactors and an artificial intelligence-powered platform to grow microalgae indoors. Its photosynthesis-based process is similar to growing algae in open ponds where they harness the light of the sun.

One advantage of producing microalgae indoors, however, rather than in the sea or open ponds, is the absence of environmental pollutants like mercury, polychlorinated biphenyls (PCBs), or pesticides, it says. Vaxa feeds the microalgae nutrients such as phosphorous, nitrogen, and carbon dioxide as inputs, which also contributes to lowering the carbon footprint of its manufacturing process.

“As our oceans change, as they become just a little bit warmer and more acidic, the algae species that are actually flourishing in our oceans shift, which has impacted even the levels of EPA and DHA that are found in fish oil,” said Corrina Bellizzi, head of sales and marketing at Örlo Nutrition in a recent podcast.

“This reveals [...] why it’s so important that we find better and more consistent sources that don’t necessarily have to impact our ocean eco-systems. That’s where, I think, we are headed in this space of omega-3s: new nutrition solutions that go directly to the source, to algae.”