Still Another Under Appreciated Supplement - Docosahexaenoic Acid (DHA)
04/01/2018 - Product Newsletter #312
As we began 2018 I was very curious about very good products that I felt did not have the sales levels they deserve, either nationally or from Moss Nutrition. As I mentioned in January, I felt that there was no question that the number one supplement that fell into that category was protein powders. However, as I have continued with my focus on behavioral and neurodegenerative disorders in the Moss Nutrition Report, I began to become aware of another grossly under-appreciated supplement specifically in relation to neurologic support. This supplement is one of the most important polyunsaturated fatty acids (PUFAs) = docosahexaenoic acid (DHA).
To hopefully increase appreciation of DHA and our product DHA 710 Select™ in relation to the epidemic of behavioral and neurodegenerative disorders, I would like to review the paper "Dietary DHA and health: cognitive function ageing" by Cardoso et al (Cardoso C et al. Nutr Res Rev, Vol. 29, pp. 281-294, 2016).
AN OVERVIEW OF DHA RESEARCH IN RELATIONSHIP TO BRAIN FUNCTION
The first quote I would like to feature from the Cardoso et al paper provides an overview of research on the impact of DHA on behavior:
"DHA, one of the most
important marine n-3 PUFA, may have a
strong influence on brain
health. Indeed, consumption of larger amounts of n-3 PUFA, particularly DHA, appears to reduce the risk of depression, including postpartum depression, bipolar disorder (manic depression), schizophrenia, and mood and behaviour disorders."
The next quote refers to both behavioral and degenerative disorders:
"It has also been hypothesized a connection between DHA in the diet and in the nerve cell membrane and the risk of dysfunction of the central nervous system in the form of anxiety, irritability, susceptibility to stress, dyslexia, stereotypic behaviour, aggressiveness, reduced learning capacity, impaired memory and cognitive functions, and extended reaction times."
The next two quotes discuss the impact of DHA on cognitive function in more detail, the first addressing from a more theoretical standpoint:
"DHA plays an important role in ensuring healthy aging, by possibly thwarting macular degeneration, AD and Parkinson's disease, and other brain disorders at the same time as enhancing memory and strengthening neuroprotection in general. A reduced level of DHA in the blood is associated with cognitive decline during ageing."
The following quote looks at the impact of DHA in healthy populations:
"Some interesting studies, either observational or randomised controlled trials (RCT), have been carried out with healthy populations. For instance, in a community-dwelling cohort, levels of α-linolenic acid (ALA), EPA and DHA were assessed in serum phospholipids (PL) of volunteers not taking fish oil supplements. It was found out that only the association between serum PL DHA and non-verbal reasoning and working memory remained after adjustment for participant education and vocabulary. Moreover, DHA increased cognitive performance in an RCT involving mentally healthy individuals older than 55 years. Daily supplementation of 900 mg of algal (Schizochytrium sp.) DHA for 24 weeks was associated with significantly lower paired associative learning errors than the placebo case. Similar results were attained by an RCT study on executive functions and neuroimaging in a group of healthy subjects whose age ranged between 50 and 75 years."
THE BIOCHEMISTRY AND PHYSIOLOGY OF DHA AS IT RELATES TO BRAIN FUNCTION
As you will see, the biochemistry and physiology of DHA is significantly different in the brain compared to the rest of the body, with emphasis on the idea that the brain preferentially favors the presence of DHA. This fact is supported by the following quote:
"For those studies involving AD patients, it has been observed that though DHA intake is low, brain DHA levels are frequently similar to controls, thus suggesting that low DHA intake leads to low plasma DHA, but does not necessarily decrease brain DHA."
The next quote provides more detail as to how important DHA is to healthy brain function:
"In the mechanistic analysis of the link between DHA and cognitive function, it should be noted that DHA is by far the main n-3 PUFA present in the brain - its content with brain fatty acids (FA) is 12-15% - where it is predominantly located in neuronal membranes of the grey matter, especially in synapses. In addition, the brain FA-binding protein preferentially binds DHA (and other n-3 PUFA), leading to higher levels of DHA incorporation in the molecular structures of the membranes."
How does DHA get to the brain? According to Cardoso et al:
"DHA is supplied to the central nervous system by the liver, where DHA attained from food is taken up and distributed to other organs. Besides, though there is evidence suggesting the expression and functional role of FA transporters at the blood-brain barrier, DHA can reach the brain by simple diffusion through this barrier."
Of course, as we all know, DHA can be made in the body from the essential fatty acid ALA, primarily found in flax seed oil. Unfortunately, this conversion does not readily occur in the human body, making DHA supplementation advisable in certain situations:
"...the dietary level of α-linolenic acid (ALA; 18:3n-3), a precursor of DHA, does not correlate well with the level of DHA in the human body, making it advisable, for instance, to supplement the nursing mother's diet with DHA."
DHA and specific brain physiology
The next quote considers the specific role of DHA in the brain:
"DHA is highly enriched in the phospholipid (PL) of the synaptic plasma membrane and synaptic vesicles. Regarding this issue, it is worth analyzing the pathways leading to the synthesis of some important PL. Phosphatidylcholine (PC), a fundamental brain PL, is synthesized through the Kennedy pathway from three precursors: choline, a pyrimidine, and, typically, a PUFA (either DHA or other PUFA). Phosphatidylethanolamine (PE) may be synthesized from a PUFA and a pyrimidine."
Of course, we are all aware of phosphatidylcholine, which can be provided as a supplement. However, while supplementation of this substance can be helpful, it is always ideal to also introduce interventions that will optimize the patient's ability to produce their own phosphatidylcholine. Therefore, it is important to note that PUFAs such as DHA are essential in this regard.
Some comments on the importance of DHA metabolites
As we all know, EPA can be metabolized to form eicosanoids such as prostaglandins that have important anti-inflammatory functions. Similarly, DHA can be metabolized to form what are known as "docosanoids":
"Differently from EPA, DHA is not a source for eicosanoid synthesis, rather exerting influence directly and indirectly. DHA can also be converted to EPA by a retroconversion reaction, thereby leading to the formation of various eicosanoid metabolites. The DHA derivatives produced by oxidation reactions also have importance and are usually termed docosanoids."
Unlike eicosanoids that have an impact on inflammation, docosanoids act as neuroprotective agents:
"Docosanoids include neuroprotectin D1 (NPD1), maresins, neuroprostanes (NeuroPs), and related 22-C derivatives. The NeuroPs are structurally related to prostaglandins and constitute a large family of oxidized cyclopentanoid derivatives."
What are important roles of docosanoids? One, NPD1, appears to play an important role in protecting against cognitive decline:
"Different mechanisms for the DHA role as a protective agent against cognitive decline have been put forward. Namely, NPD1 may support brain cell survival and repair through neurotrophic, anti-apoptotic and anti-inflammatory signaling. Indeed, many of the effects of DHA on the neurological system may be related to signaling connections..."
In completing this discussion on docosanoids, it should be pointed out that NSAIDs such as aspirin, which are known to inhibit pro-inflammatory arachidonic acid byproducts via inhibition of cyclooxygenase, can also inhibit important docosanoids:
"...it has...been shown that lipoxygenase inhibitors block the synthesis of many docosanoids."
DHA and inflammation
Of course, no discussion on DHA would be complete without a mention of the function of DHA with which we are most familiar, as an anti-inflammatory. Concerning the role of DHA and inflammation as it relates to neurologic activity, Cardoso et al state:
"A further mechanism relating to DHA dietary intake and cognitive function ageing may involve the role of DHA in inflammatory processes. Indeed, DHA and EPA are deemed to display some anti-inflammatory properties, thereby offsetting the pro-inflammatory effects of n-6 PUFA."
The authors continue with a discussion of the specific mechanism of the anti-inflammatory activity of DHA:
"The DHA-derived docosanoids are potent endogenous anti-inflammatory and pro-resolving chemical mediators. They may reduce chronic inflammation by attenuating NF-kB, thereby modulating the expression of pro-inflammatory cytokines."
DHA and cell membrane activity
Another important function of DHA as it relates to neurologic function occurs via an impact on cell membranes:
"...DHA incorporation into cell membranes modulates the efficiency of numerous membrane transporters and enzymes. The incorporation of DHA into cell membranes is of great importance, since many essential cellular processes take place in and on membranes."
DIETARY SOURCES OF DHA
The next section of the Cardoso et al paper I would like to feature discusses dietary sources of DHA. Of course, the primary source is seafood:
"Oily fish, such as herring, salmon and sardine, are the richest sources of DHA. According to these authors, of thirty-seven commonly consumed types of fish products, DHA is the main n-3 PUFA being on average 65% of total n-3 PUFA. It should be remarked that DHA content in fish usually varies with the overall n-3 PUFA content. Three main classes of fish products may be differentiated on the basis of DHA content: relatively poor DHA sources (black scabbardfish, catfish, hake, megrim, tilapia); moderately rich DHA sources (halibut, Pollock); and very rich DHA sources (herring, mackerel, salmon, sardine), corresponding to the approximate ranges <300, 300-500, and >500 mg/100 g, respectively."
"The six highest DHA contents are found in the European eel, chub mackerel, Atlantic salmon, Atlantic mackerel, gilthead seabream (wild) and sardine, all exceeding 1000 mg/100 g."
Concerning specific dietary recommendations, Cardoso et al recommend the following:
"A single weekly meal of 150 g of chub mackerel, Atlantic salmon or sardine may be more than enough to meet...DHA RDI (250 mg/day). For seafood moderately rich in DHA, the consumption of two to three weekly meals of 150 g may also be enough."
However, as noted in the next quote, ingestion of optimal amounts may not equate to bioaccessibility:
"The level of DHA in a portion of food that is eaten may be quite different from the bioaccessible level, that is, the DHA concentration that is released from the food matrix into the intestinal lumen after digestion and is available for absorption."
Therefore, with the assumption that many, if not most, of our patients will demonstrate suboptimal digestive and absorptive capacity at some level, supplementation may be necessary even with ideal dietary DHA intake.
MORE INFORMATION ON THE ABILITY OF THE BODY TO PRODUCE DHA
As was briefly mentioned above, even though DHA can be produced from ALA in the body, this pathway is not particularly efficient. This pathway is discussed in more detail in the next quote:
"Besides dietary DHA and the bioaccessibility/bioavailability issues, DHA may be biosynthesized in the human body. However, for healthy and non-vegetarian humans, despite the availability of the necessary enzymes, there is extremely limited synthesis of DHA in adults. Unless induced by several years of a vegetarian diet, the human enzymatic machinery is very inefficient in converting, for instance, ALA to EPA and DHA. Even with a diet deficient in DHA, the brain cells' ability to synthesise DHA from ALA is very low. One study indicates a very low share of plasma ALA (below 0.2%) is deployed to the synthesis of DHA via EPA. Indeed, it has been claimed an extremely low level of conversion of the precursor ALA to EPA, <5%, and to DHA, <0.05%. Several enzymes are required to elongate and desaturate ALA or other shorter and less unsaturated n-3 PUFA into DHA. Research has found evidence suggesting that DHA formation may be regulated independently of other FA in the pathway and that DHA binding to PPARα suppresses transcription of the delta-6 desaturase gene, thereby down-regulating conversion of ALA to DHA. Indeed, it should be noted that the rate-limiting step in DHA synthesis is precisely the desaturation of ALA by delta-6 desaturase."
Therefore, despite the belief by many in the nutritional community that ALA found in flaxseed oil can act as a good source of DHA via endogenous conversion, a large volume of research emphatically suggests otherwise.
SOME FINAL THOUGHTS
The last quote I would like to feature from the Cardoso et al strongly notes that, even though DHA is not an essential fatty acid, its dietary intake is essential for optimal human health:
"The large importance of DHA makes this an essential FA in human nutrition."
Of course, as I mentioned in the beginning of this monograph, sales of our DHA 710 Select™ indicates that far too few clinicians and patients are aware and/or recognize the importance of dietary DHA, particularly in relation to behavioral and neurodegenerative issues. Hopefully, this newsletter will be a catalyst for the reversal of this trend.
DHA 710 Select™ 90 SG from Moss Nutrition
Total Omega-3 Fatty Acids 780 mg
DHA 710 mg
EPA 50 mg