CLINICALLY PROVEN;

• Supports foetal neuronal development and newborn neurobehaviour

• Improves foetal growth and development 

• Shown to inhibit foetal pro-inflammatory genes

• Plays a vital role in protecting and building brain structure

• Paramount to the physiological development of photoreceptors (visual development and function).

• Improves foetal cardiac autonomic control 

• Defends against infant cognitive and locomotor deficits

• Regulates brain cell survival and repair

• Associated with improved attention and memory span

• Improves cognitive scores in under-developed children

• Actively antagonises inflammation and promote disease resolution

• Beneficial against Rhematoid Arthritis and existing Cardiovascular disease

• Reduces platelet aggregation, reducing the risk of developing cardiovascular disease 

MICROALGAE OMEGA 3

Omega-3 fatty acids (LC-PUFA), including DHA and EPA, are chiefly obtained from oily deep-water fish.[6]Highly sought after for its health promoting benefits, the increasing demand for this commodity is accompanied by escalating concerns of sustainability and contamination of the supply. Accordingly, the planet is faced with declining fish reserves, emphasising the need for a viable alternative to bear the weight of this growing predicament.[7]

Interestingly, fish do not synthesise these fatty acids de novo as they lack the required key enzymatic activities to do so. Instead, fish obtain EPA and DHA from a diet of microalgae,[8].

Algal oil, derived from microalgae Schizochytrium provides a renewable plant-based source of DHA and EPA that is low in impurities,[1] offering a high quality and unpolluted alternative that is safe for use within prenatal care. 

Commercially cultivated in open ponds, microalgae is rapidly grown in culture where tons of carbon dioxide is removed from the atmosphere for each ton of oil produced, making the cultivation process environmentally friendly.[13]

Microalgae crops do not compete for land space and adapt their metabolism to heterotrophic[†]conditions; simply requiring sunlight exposure to photosynthesise.[14]

Further, microalgae-derived omega-3 EFAs extend the benefits of DHA and EPA to those following a vegan or vegetarian lifestyle; a demographic commonly lacking in these nutrients.[2] Comparative studies have highlighted that DHA and EPA from algae are functionally the same as fish-derived EFAs in their ability to optimise omega-3 status.[3],[4]

PREGNANCY

Key developmental stages within the human lifecycle also require an increased need for DHA. Specifically, the last trimester of pregnancy leading into the first 18 months of life are critical periods that necessitate increased intake;[22]with appropriate DHA supply playing a vital role in infant development, particularly for the structure and function of the brain and eyes.[23] 

Whilst newborns are capable of synthesising DHA from ALA, they generally cannot produce enough to meet physiological demands and prevent declines in cellular DHA concentrations; thus they depend upon maternal provision.[24] 

The last trimester of pregnancy is the most active period of foetal brain cell division. Further, brain weight has been found to increase from approximately 100 g at 30 weeks of gestation to around 1,100 g at 18 months of age, increasing the DHA content within the brain from 90 mg to 3,300 mg.[25] 

Observational studies associate higher intakes of omega-3 LC-PUFAs during pregnancy with improved foetal growth and development during gestation. In a double-blind, placebo-controlled trial, 350 pregnant women aged between 16-35.9 years were assigned to receive algal oil, containing 600 mg/d of DHA, or placebo. 

Supplementation occurred from 20 weeks of gestation, through to birth. Compared with placebo, the algal oil intervention group scored significantly higher in maternal and cord red blood cell (RBC)-phospholipid-DHA concentrations (p=0.001), longer gestation duration (p=0.041), greater birth weight (p=0.004), greater length (p=0.022), and increased head circumference (p=0.012).[50] 

In addition, the algal oil group had fewer infants born before 34 weeks of gestation (p= 0.025), and shorter hospital stays for infants born preterm (p= 0.026).[51]These results indicate that DHA accumulation during pregnancy, using algal oil, corresponds with improved birth outcomes for infants relative to growth and development.[52]

Additionally, algal oil was shown to improve foetal cardiac autonomic control and newborn neurobehaviour, in a longitudinal, double-blind, placebo-controlled study. 

Forty-six pregnant women aged 16-35.9 years were randomised to receive either algal oil, containing 600 mg/d of DHA, or placebo from 14.4 (+/-4) weeks gestation through to birth. In addition to maternal and foetal blood collection, foetal heart rate variability (HRV) was measured as an indicator of cardiac pacing and autonomic nervous system (ANS) integrity (a higher HRV is associated with a responsive and flexible ANS). 

Post-hoc comparisons indicated a significant increase between baseline and post-partum maternal RBC DHA (p=0.0001) and plasma DHA (p=0.0004) within the algal group, and when comparing the algal and placebo groups for RBC (p=0.0006) and plasma DHA (p=0.010).[53]Newborn RBC DHA was also significantly higher in the supplemented group (p=0.015).[54] 

Furthermore, infants from women randomised to the algal oil intervention showed significantly higher (i.e. more optimal) scores on the motor (p=0.038) and autonomic clusters (p=0.029) of the Neonatal Behavioral Assessment Scale (NBAS), reflecting improved function in neurobehavioural domains.[55]

SUPPORTS FOETAL NEURONAL DEVELOPMENT

Highly concentrated in DHA, algal oil supports the physiological requirements of DHA for foetal and newborn development. During gestation, DHA is transported across the placenta, where it is then released into circulation.

The role of DHA during foetal and infantile brain development is proposed to act on multiple levels, encompassing membrane biogenesis, gene expression, protection against oxidative stress and neurotransmission support:

• DHA directly interacts with membrane proteins within the cellular lipid bilayer to facilitate signal transduction, neurotransmission, and formation of lipid rafts[‡].[27]

• Unesterfied DHA has roles in regulating gene expression and ion channel activities, and can be further metabolised to form neuroprotective metabolites within brain tissue.[28]

• DHA acts as a precursor for neurogenesis, whilst also influencing phospholipid synthesis and turnover.[29]Deficiency has been shown to negatively impact neurogenesis, neuronal migration and outgrowth. Disrupted neurogenesis also contributes to altered monoamine and cholinergic neurotransmitter systems.[30]

• DHA has been shown to inhibit oxidative stress induction of pro-inflammatory genes, and apoptosis in the brain and retina. The free radical scavenging properties of DHA have protective effects on lipids and proteins within brain tissue, shielding against perioxidative damage, neuronal loss, and subsequent cognitive and locomotor deficits.[31]

Beyond the important role of protecting and building brain structure, DHA is also integral to foetal eye development, and maintaining retinal health. The physiological function of the rods in retinal photoreceptors are DHA dependent, and contain an exceptionally high content within their membranes. 

DHA gathers around the protein, rhodopsin, which receives external light signals. Upon receiving these signals, rhodopsin undergoes a conformational change that initiates a signal transduction cascade, converting light into electrical signals for visual processing.[32] 

The presence of DHA within the membrane facilitates this biochemical change, with studies demonstrating highly saturated membrane bilayers to be superior in function to those with fewer DHA molecules.[33] Figure 4 highlights the mechanistic actions of DHA within retinal photoreceptors.

The prevalence of DHA within retinal photoreceptors, in addition to its physiological actions within cell membranes, emphasises that adequate supply of DHA is paramount to neurological and visual development and function.

SUPPORTS NEURONAL FUNCTION

In the brain, algal oil is beneficial for cognition and behavior due to its function within neuronal membranes.[35] 

Its DHA constituent builds brain structure; contributing to 30% to 40% of the total LC-PUFAs within grey matter of the cerebral cortex. Additionally, DHA is involved in multiple processes that support neuronal health.[36]

For instance, DHA sustains phospholipid reservoirs within neuronal membranes for the synthesis of lipid messengers. In turn, these messengers prompt signalling cascades that either promote neuronal injury and apoptosis or enhance neuroprotection and repair.[37]

The neuroprotective benefits of DHA are mediated through its role as a precursor of oxygenation products, known as docosanoids, which are powerful anti-inflammatory mediators. Specifically, the mediator 10,17S-docosatriene (neuroprotectin D1, NPD1) has shown to counteract leukocyte infiltration, nuclear factor-kappa β activation, pro-inflammatory gene expression, and is an apoptostatic mediator that counters oxidative stress-triggered DNA damage of cells.[38] 

Through these mechanisms, DHA derived NPD1 homeostatically regulates brain cell survival and repair involving neurotrophic, antiapoptotic and anti-inflammatory signalling. Further, NPDI has regulatory interactions with molecular-genetic mechanisms involved in beta-amyloid precursor protein and amyloid beta peptide; implicated in physiological and pathological processes that affect neuronal functioning and cognition.[39]

Highly concentrated in DHA, algal oil supports the physiological requirements of DHA for foetal and newborn development.

Additionally, studies have identified that DHA supports the functional integrity and resilience of cortical neurons.[40]Required for astrocyte maturation and vascular coupling, and cortical glucose uptake and metabolism, sufficient DHA status encourages neuronal maturation, synaptogenesis, and grey matter expansion. These are positively associated with neurocognitive development trajectories, particularly involving attention and memory.[41]

Lastly, algal oil’s DHA molecule plays a supporting role in optimal functioning of the myelin insulating layer surrounding nerve fibers.[42]If the available DHA is insufficient during active phases of myelin synthesis, propagation of the myelin sheath is metabolically blocked, resulting in a malformed or defective sheath (dysmyelination) or breakdown of the myelin sheath (demyelination).[43] 

Consequently, this leads to under functioning within signal transduction pathways and neurotransmission, thus compromising overall neuronal functioning. Conversely, sufficient DHA availability enhances synthesis of the myelin insulating layer, improving its efficiency.[44]

COGNITION AND BRAIN FUNCTION

Algal oil has been shown to improve cognitive function amongst older adults with age related cognitive decline. Randomised to receive either 900 mg/d of DHA from Schizochytrium or placebo, the benefits of algal oil were demonstrated in a double-blind, placebo-controlled clinical study consisting of 485 participants aged ≥55 years. The 24 week study utilised the Cambridge Neuropsychological Test Automated Battery (CANTAB) in conjunction with the Paired Associate Learning (PAL) test; assessing memory, learning, attention and problem solving.

Significant improvements were demonstrated in the algal group, regarding immediate and delayed verbal recognition memory scores (p=0.02), in addition to showing significantly fewer test errors between baseline and final testing (p=0.032).[56] Furthermore, plasma levels of DHA doubled throughout the treatment period, with the increase significantly correlating with improved testing scores (p=0.02).[57]Thus, results from this study demonstrated that 900 mg/d of DHA from algal oil improved episodic memory and learning in healthy adults with mild memory complaints. 

Authors of this study noted that these advances yielded an equivalent seven year improvement in testing performance after intervention.[58]

Further to this, a randomised, double-blind, placebo-controlled trial investigated the effects of algal oil supplementation for 16 weeks on children’s cognitive functioning. Using 600 mg/d of DHA derived from algal oil or placebo, 362 school children aged between seven and nine years were selected based on reading underperformance (≤33rd centile). 

Outcomes of the intervention were assessed using the age-standardised Word Reading Achievement sub-test of the British Ability Scales (BAS II). Significant benefits from DHA supplementation were seen in 224 children whose initial reading performance was ≤20th centile (p=0.04), and these benefits were more pronounced in children whose initial reading performance was ≤10th centile (p=0.01) (Figure 5).[59]

Based on these findings, supplementation with algal oil was found to be effective in improving reading scores in underperforming children[60]; supporting its use in improving cognitive function.

ANTI-INFLAMMATORY

Inflammation is a key driver behind many chronic disease states, including rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, asthma and psoriasis.[45] 

DHA rich algal oil has been shown to reduce inflammation by targeting the chemical mediators involved in the inflammatory response, including prostaglandins, thromboxanes and cytokines released through the cyclooxygenase-2 (COX-2) pathway.[46]

This anti-inflammatory action primarily occurs through infiltration of DHA and EPA components into cell membranes in place of arachidonic acid (AA).[§] This interchange leads to alterations in signaling molecules, known as eicosanoids, which down-regulate production of pro-inflammatory mediators. 

Specifically, algal oil has been shown to reduce 5-lipoxygenase (5-LOX), leukotriene B4 (LTB4), 5-hydroxyeicosatetraenic (5-HETE), thromboxane B2 (TXB2), tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α) and IL-1β; all of which function as biomarkers of inflammation.[47], [48]

Reinforcing this further, DHA and EPA undergo conversion through a series of reactions to form pro-resolving mediators, termed resolvins, protectins and maresins, which actively antagonise inflammation and promote resolution.[49]

INFLAMMATORY CONDITIONS

The clinical benefits of algal oil for reducing inflammation were demonstrated in a double-blind study consisting of 38 participants with defined rheumatoid arthritis (RA). 

Individuals were allocated to consume foods enriched with algal oil from Schizochytrium (equivalent to 2.1g DHA/d) for 10 weeks, followed by a 10 week crossover period receiving placebo. The daily consumption of algal oil led to a significant decline in the sum of tender and swollen joints (p=0.010), compared with placebo.[62] 

Plasma concentrations of AA-derived TXB2 significantly declined (p=0.035), along with the capacity to convert AA to the pro-inflammatory 5-LOX product, 5-HETE (p=0.012).[63]Additionally, levels of the DHA-derived maresin /resolving precursors,14-/17-hydroxydocosahexaenoic acid (14-/17-HDoHE), significantly increased during supplementation (p<0.05), which correlates with the resolution of inflammation.[64] 

Findings from this study demonstrate that supplemental microalgae ameliorates disease activity in patients with RA, along with a shift in the balance of AA and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.

Comparably, another study involving 34 moderately hyperlipidemic men examined the effects of microalgae-derived DHA on inflammatory markers associated with cardiovascular disease. 

Using a double-blind, placebo-controlled design, participants were randomised to receive either algal oil containing 3 g/d of DHA or placebo for 90 days. Blood samples taken after 45 days of intervention and at study conclusion showed a significant decrease in the number of circulating white blood cells by 7.2% and 6.4% respectively, compared with baseline measurements (p=0.05).[65]

This finding was primarily due to a decrease in the number of circulating neutrophils by a corresponding 11.7% and 10.5% (p=0.05).[66]

Additionally, a decrease in inflammatory markers was noted, with C-reactive protein (CRP) concentrations reducing by 15% (Figure 6), IL-6 by 23%, and granulocyte monocyte-colony stimulating factor by 21%. An increase in anti-inflammatory matrix metalloproteinase-2 (MMP-2) by 7% (p=0.05) was also seen;[67] supporting the role of algal oil in reducing inflammation.

CARDIOVASCULAR DISEASES

Supported by numerous studies, fish oil helps attenuate the drivers behind cardiovascular disease risk, including hypertriglyceridemia. 

One such study examined the comparable effects of microalgae derived from Schizochytrium to that of fish oil. In this double-blind, parallel trial, consisting of 86 subjects with hypertriglyceridemia, participants were randomised to receive either algal oil, fish oil or placebo for 14 weeks, with ingestion of algal oil providing 1,172 mg/d of DHA and 656 mg/d of EPA. 

Compared to placebo, triaglycerol (TAG) levels significantly decreased from baseline to treatment end for both algal oil and fish oil groups (18.9% and 22.9%, representing p=0.001).[69] 

Authors of this study noted that the reduction in TAG levels in the algal oil intervention group was comparable to those seen within the fish oil group, highlighting that microalgae oil has equivalent efficacy to fish oil for managing hypertriglyceridemia.[70]

Further, microalgae oil has been shown to exert protective effects against cardiovascular events through its anti-platelet and antioxidant properties. In a study involving 12 male volunteers with a mean age of 58.1 years, subjects were supplemented with algal oil containing doses of DHA that increased incrementally at two weekly intervals. 

The total intervention period comprised of eight weeks, commencing with a dosage of 200 mg/d DHA until reaching a concluding dose of 1,600 mg/d of DHA from algal oil.

Platelet aggregation and reactivity significantly decreased after 400 mg/d of DHA was reached, whilst 800 mg/d of DHA yielded a more significant (70%) reduction in platelet aggregation (p≤0.05).[71]

Algal oil intake was found to alter the production of COX-2 product, TXB2, with a significant decrease observed with 400 mg/d and 800 mg/d DHA (p=<0.05).[72]Platelet vitamin E concentrations also increased after 200 mg/d DHA (p=<0.05).[73]

These results demonstrated microalgae oil supplementation induced antiplatelet and antioxidant results. Given that platelet aggregation and oxidation are involved in the pathogenesis of several cardiovascular conditions, including hypertension, hypertriglyceridemia, thromboembolic disorders, atherogenesis and coronary artery disease, these benefits may prove beneficial in reducing overall cardiovascular disease risk.[74]