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InFocus

How can DHA dietary supplementation support brain development in pets?

Evidence shows that docosahexaenoic acid (DHA) dietary supplementation during the pre- and post-natal period can support brain and vision development in growing cats and dogs, as well as cognitive functions in puppies

Omega-3 fatty acids – eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular – are key dietary components that contribute to the health and well-being of cats and dogs. They are required for various body systems, including the skin, coat, retina, brain and immune system. While nutrition is not the only source of brain DHA – studies have shown that dietary supplementation is effective in supporting retinal and brain functions in pets. In fact, studies conducted with puppies have shown a positive impact of DHA dietary supplementation during gestation and/or the first months of life on some cognitive tasks.

Currently, most of the products providing DHA available on the market contain fish oil as an ingredient of origin. Because of the sustainability challenge, other alternatives should be considered to secure planet resources while supporting the healthy development of our pets. DHA from marine microalgae represents an interesting solution, reinforcing the interest in this nutrient when developing a nutritional programme for the early stages of life.

The role of DHA

N-3 polyunsaturated fatty acids (n-3 PUFAs), especially EPA and DHA, have been proven to act positively on a panel of human health conditions through interesting antioxidative and anti-inflammatory properties. Several health benefits have also been described in pets. A dietary source is mandatory when animals cannot synthesise de novo n-3 PUFAs or produce them from their precursors in large enough quantities.

Brain development and retinal function

After adipose tissue, the nervous system is the organ with the highest concentration of fats. DHA is the major n-3 PUFA in the brain, comprising 30 to 40 percent of the aminophospholipid fatty acids in neuronal cell membranes. As an integral component of neural cell membranes, DHA is involved in numerous processes, such as membrane order, receptor activation and signal transduction, to name a few.

The brain can also take up blood DHA synthesised in other tissues, but plasma enrichment of the newly synthesised DHA does not compare to that obtained from preformed DHA in the diet

Nutrition is not the only source of brain DHA, as the brain can produce DHA from alpha-linolenic acid (ALA), docosapentaenoic acid (DPA) and EPA. The brain can also take up blood DHA synthesised in other tissues, but plasma enrichment of the newly synthesised DHA does not compare to that obtained from preformed DHA in the diet. Nevertheless, during the developmental phase, the needs are so important that dietary supplementation is required to support the organs.

An overview of early brain development in puppies

FIGURE (1) The average puppy brain development in percentage compared to the average brain adult size (Arant and Gooch, 1982; Coppinger and Coppinger, 2001)

Brain development starts during the in utero phase and continues during the first weeks and months of life, with a progressive increase in the organ size and a maturation of the connections when growth slows down (Figure 1). Neurulation appears to begin at approximately days 15 to 17 of gestation in the dog. By 28 days post-coitus, the telencephalic vesicles have formed, developing rapidly from approximately day 19/20 onward. At 55 days post-coitus, major brain structures are readily recognisable counterparts of their adult form.

Regions of the brain develop at different rates throughout early life, thus potentially remaining susceptible to environmental exposures. While some stressors, nutritional deficiencies or teratogenic factors may have deleterious effects in the short and long term, other environmental factors, such as maternal care or dietary supplementation, may promote healthy neurological development (Gaillard et al., 2022).

What is the role of DHA in canine brain and ocular development?

Studies over the last decade have provided evidence that a deficiency of DHA leads to nervous system abnormalities, such as decreased visual acuity, electroretinographic abnormalities, polyneuropathy and reduced learning ability (National Research Council, 2006).

In the retina, DHA is incorporated primarily into structural glycerophospholipids of the cell membrane lipid bilayer and accounts for an important part of the total polyunsaturates in the mammalian retina. The acid is particularly concentrated in the disc membranes of the rods’ outer segments, where it accounts for up to a third of the total fatty acids. DHA also plays an essential role for photoreceptor cells in the acquisition of visual function. Dietary DHA modulates the maturation and survival of photoreceptor cells, and animals fed polyunsaturated-fatty-acid-free diets during growth develop abnormal electroretinograms (ERG) with decreased retinal DHA contents (Pawlosky et al. 1997).

There is also evidence that feeding dams diets enriched with fish oil during gestation and lactation improves ERG-recorded retinal activity in their puppies (Heinemann et al., 2005). Feeding diets fortified in DHA through fish oil supplementation has also led to higher peak b-wave during scotopic ERG (Zicker et al., 2012).

Does DHA supplementation affect the cognitive performance of puppies?

Several studies (Table 1) have described the cognitive performances of puppies after DHA dietary supplementation of the dams (Kelley and Lepine, 2005) and/or the puppies (Hoffman et al., 2007; Zicker et al., 2012; Kelley and Lepine, 2014), as well as with DHA and ALA supplementation (Reynolds et al., 2006).

Period of dietary supplementationAge at testing (weeks)DosageEffectCommentsReference
From weaning to 52 weeks

Sixteen puppies per group (from 14 litters)
8 to 520.19 percent DHA on dry matter (compared to
0.095 and 0.01 percent)
Positive effect on bones, joints and psychometric and cognitive tasks with DHA supplementation
 
Positive effect on vaccine response with the highest dose
Higher levels of vitamin E, taurine, choline and L-carnitine in the DHA-rich diet.


DHA was given in maternal diet during gestation up to weaning at 0.01 percent
Zicker et al. (2012)
From 3 to 16 weeks

Twenty puppies per group (from five litters)
8 to 161 percent DHA with 2 percent ARA of the total fat intake (compared to 2 percent corn fat of the total fat intake)Positive effect on cognitive tasks with n3-PUFA supplementationReynolds et al. (2006)
From dams’ pregnancies to nine weeks old


Eight puppies per group
7 to 90.18 percent DHA on dry matter (compared to 0.01 percent)Positive effect on cognitive tasks with DHA supplementationKelley and Lepine (2005); Kelley (2022)
From dams’ pregnancies to 14 weeks old
 
Twenty puppies per group (from 28 litters)
10 to 150.135 percent DHA on dry matter (compared to 0.77 and 0.015 percent)Positive effect on cognitive tasks with the highest dosage when compared to the lower doseSee Figure 2 for resultsHoffman et al. (2007); Kelley (2022)
From weaning to 25 weeks


Twelve puppies per group
15 to 250.135 percent DHA on dry matter (compared to 0.015 percent)Positive effect on cognitive tasks with DHA supplementationDiet not supplemented during gestation up to weaningKelley and Lepine (2014); Kelley (2022)
TABLE (1) A summary of different cognitive studies performed in puppies, including test conditions and main findings

As brain structure development starts in utero, some studies were interested in starting DHA supplementation before gestation. For instance, in Hoffman et al. (2007), 28 dams received different levels of DHA supplementation from the onset of proestrus. Females were fed their assigned diet throughout gestation and lactation, and their puppies were weaned on the same diets. At nine weeks old, puppies were trained with a visual and spatial discrimination task, where a specific reinforced visual target was placed in one arm of a T-maze. A series of 10 trials was then conducted daily until the puppies reached the threshold of 8 out of 10 successful trials in two consecutive sessions. After they reached the threshold, their performance was assessed on a reversal task (the reward location was switched to the other arm) with a dose-dependent response trend (Figure 2).

FIGURE (2) T-maze success in puppies enriched with low, medium or high DHA diets tested between 10 and 15 weeks of age (Hoffman et al., 2007)

But as the brain continues its development and maturation after birth and even after weaning, some researchers looked at the effect of late (post-weaning) dietary intervention. For instance, in Zicker et al. (2012), 48 puppies weaned at two months from mature dams were fed a commercially available low-DHA food and assigned to one of three groups. Each group was fed a different DHA content diet for 10 months, during which several biological, physiological and cognitive parameters were evaluated. Among the significant differences found was the fact that the puppies receiving DHA supplementation performed better in some of the reversal and landmark tasks, with less error for the group receiving the highest dose.

What do these studies show?

Different levels of DHA dietary supplementation led to differences in some of the physiological and cognitive parameters assessed by the above studies. In general, puppies fed on higher DHA dosages have a higher DHA serum level and performed better than their conspecifics on the paradigm tested. DHA dietary supplementation during pregnancy and the post-natal period of the dam, or even only after weaning, also helps support some cognitive performances in puppies.

Different levels of DHA dietary supplementation led to differences in some of the physiological and cognitive parameters assessed

The underlying mechanisms of the beneficial effects of DHA on cognitive function are not yet fully understood. However, the evidence of DHA contributing to synaptic membrane fluidity, enzymatic mechanisms and the production and expression of dopamine receptors highlights the role this nutrient can have in several stages of neural development in the foetus and newborn. It should also be noted that  the same n3-PUFAs are the main constituent of the phospholipid membrane of reproductive tissues and gametes.

Finally, it is important to consider that factors other than nutrition will directly (or indirectly) impact cognitive performance. This might include genetic, environmental (nursing, socialisation, enrichment, etc) and training factors, for example.

Does DHA supplementation have the same effect on kittens?

An overview of early brain development in kittens

FIGURE (3) The relative growth of kittens’ brains according to body development in relation to age (Packard, 2021)

Studies show that kittens’ brain structures grow in volume at a rapid pace, starting even during the prenatal period. The development of the feline brain follows the path of an exponential curve (Figure 3), with the brain growing rapidly relative to the body early in ontogeny and attaining maximum mass well before the body reaches its maximum (Packard, 2021). Therefore, at birth, the brain is about 20 percent of the adult size.

While the neocortex size increases and reaches the adult size rapidly, white matter grows at a slower pace, reaching adult volume at around four months old (Hovda et al., 2006). All brain structure and metabolism then continue maturing until adulthood.

What is the role of DHA in feline brain and ocular development?

In cats, DHA accumulates in the brain throughout their life and can be synthesised if needed; however, this is poorly efficient (Pawlosky et al., 1994).

In juvenile felines (during the first eight weeks of life and even during pregnancy), maintaining DHA status in the nervous system is important for optimal retinal function (Pawlosky et al., 1997). Kittens can use some precursors (ALA) in the milk to synthesise n3-PUFAs, but this is not enough to cover their high needs. Queens are unable to produce the proper levels of EPA and DHA in milk, so feeding kittens the precursors of those fatty acids is essential. If gestating queens and kittens directly receive EPA and DHA, the levels of those acids in the brain are higher in kittens (Pawlosky et al., 1997).

So far, there is no scientific demonstration that DHA dietary supplementation positively impacts the cognitive performances of kittens, mainly because testing cats in a controlled setting poses a challenge. Nevertheless, based on the similarity of organogenesis, physiology and anatomy with dogs, we can extrapolate that DHA supplementation during early life can be beneficial for the cognitive development of kittens.

The origin of the nutrient – sourcing DHA for supplementation

Although neonates can synthesise n-3 PUFAs from ALA, it remains uncertain whether such a conversion is sufficient to meet the demands of rapidly developing neural tissues. While delivery of n-3 PUFAs to the foetus occurs through placental transfer, the principal source of n-3 PUFAs for newborns is the maternal milk. Thus, maternal dietary n-3 PUFA intake during gestation and lactation directly impacts the n-3 PUFA status and subsequent brain development of the foetus and neonate.

Sourcing DHA sustainably

Currently, the supply of n-3 PUFAs (EPA, DHA) added to complete diets comes mainly from capture fisheries. However, this source may not only threaten our ecosystem, thus impacting biodiversity, but also compete with the human food chain. Global warming and overfishing lead to stock reduction, with a fishing industry that quite often threatens human rights.

There are opportunities to upcycle unused by-products from the fish filleting industry involved with the human food chain. It is also possible to secure supply from independent third-party-certified sustainable sources, such as the Marine Stewardship Council (MSC) and the International Fishmeal and Fish Oil Organisation (IFFO). But even these solutions may not be ideal in the long term.

By going a step back in the marine food chain, we can find the microalgae producing EPA and DHA from smaller polyunsaturated fatty acids. This option sounds promising

Even using alternatives such as lower trophic level species like zooplankton, krill or copepods presents the same challenges. But by going a step back in the marine food chain, we can find the microalgae producing EPA and DHA from smaller polyunsaturated fatty acids. This option sounds promising, as it consists of removing intermediate steps in the usual production chain, with marine microalgae being the natural source of fatty acids for fish (Remize et al., 2021).

Is microalgae the way forward?

Microalgae are single-cell aquatic organisms that use sunlight or nutrient calories as an energy source for growth. Most can be cultivated, securing the quality of the supply while impacting less on the ecosystems or on precarious human working conditions. Quality parameters and the consistency of the nutrient composition will be guaranteed through a strictly controlled production process.

As knowledge and technologies progress in the coming years, other dietary ingredients will be sourced in a more sustainable way. In fact, several studies conducted in pets already provide evidence that n-3 PUFAs sourced from microalgae not only are safe (Dahms et al., 2019; Vuorinen et al., 2020), but also bring health benefits: acting positively on immunity (Souza et al., 2019), inflammatory responses (Souza et al., 2019, 2020; Scheibel et al., 2021), vision (Risolia et al., 2018) and cognitive decline (Hadley et al., 2017).

Conclusion

Brain structure appears quite early during the developmental phase in cats and dogs, with an exponential growth of the structures in parallel to the accumulation of DHA. This is because DHA plays an important role in the membrane composition and function of the brain and retina.

There is evidence that either deficiency or dietary supplementation of DHA can impact the normal development of kittens and puppies, with an effect on vision and cognitive performances. Research also demonstrated that DHA dietary supplementation during pregnancy and the post-natal period of the dam, as well as only after weaning, helps support some cognitive performances in puppies.

From a sustainability point of view, DHA from microalgae oil represents an interesting alternative to fish oil. The hope is to reduce the impact on the ecosystem while providing health benefits to our pets. Therefore, in the coming years, we may have not only additional demonstration of the benefits of this nutrient, but also updated knowledge and technology to source it more sustainably.

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