Compound-specific isotope ratio analysis challenges beliefs we ’ ve long held , derived from blood measurements , that shortchain omega-3s ALA and SDA cannot contribute to DHA requirements .( 17 ) Though these short-chain omegas don ’ t meaningfully raise DHA in circulating RBCs or plasma , research suggests they do biosynthesise to new tissue DHA in the brain and liver efficiently . Researchers at the University of Toronto recently showed whole body ( including liver and adipose ) DHA accrual rates from dietary ALA to be up to 47 times higher than in circulating cells .( 18 ) The highest known natural source of omega-3 SDA , refined Buglossoides arvensis seed oil , when trialled against flax and a pure marine DHA source , demonstrated comparable tissue DHA turnover rates compared to a pure marine DHA source . Previous work established that , based on ALA- > DHA synthesis rates in rodents and humans , that despite being conducted in rodents , this work is confidently transferrable to humans .( 19 ) Pioneers of the omega-3- index test , OmegaQuant , acknowledged recently that this research “ means that the Omega-3 Index , which tests EPA and DHA levels by percentages in red blood cells , may not be the most appropriate test for ( refined Buglossoides arvensis seed oil ’ s ) contribution to overall omega health and wellness benefits .”( 20 )
Preformed DHA controversy in clinical outcomes
While clinicians typically appraise omega status through the elevation of DHA in red blood cells , due to ease of measurement , the University of Toronto ’ s groundbreaking research raises the question of why plant-based omegas readily raise EPA but not DHA in the blood , despite appearing to be far more adequate in maintaining tissue DHA in a healthy developed brain than previously believed .( 17 ) Could there be advantages to enriching DHA directly into key tissues , as opposed to raising blood levels , particularly as relate to cardiovascular outcomes ? Several clinical trials and meta-analyses suggest that direct DHA ingestion , in contrast to EPA , can raise LDL cholesterol , even undermine plasma
EPA ’ s protective effects against major adverse cardiovascular event risk , and potentially increase the risk of atrial fibrillation .( 21-27 ) The most recent NHANES data likewise showed only higher serum EPA ( not DHA ) to correlate to lower cardiovascular death risk .( 28 )
A three-month double-blind , randomised , placebo-controlled , crossover trial in middle-aged men and women found 0.7g DHA / day to increase LDL cholesterol by 7 %.( 21 ) Furthermore , LDL cholesterol : ApoB ratio was 3.1 % higher with DHA treatment than placebo , suggesting an increase in LDL size . The authors hypothesised that DHA downregulates the expression of the LDL receptor . A meta-analysis of 21 studies likewise found fish oil supplementation , though associated with a significant reduction in triglycerides , to be associated with an average 6mg / dL increase in LDL-C levels .( 22 )
Recent research also suggests that DHA may reduce the cardioprotective effects of EPA . A meta-analysis of eight eligible studies including 57,754 participants revealed DHA to increase LDL cholesterol , while EPA decreased LDL cholesterol .( 23 ) EPA and statins were shown to improve endothelial dysfunction and protect against HDL oxidation , but DHA did not . An article entitled “ Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events ” studied 987 randomly selected subjects from the INSPIRE biobank registry who underwent coronary angiography .( 24 ) Rapid throughput liquid chromatographymass spectrometry quantified EPA and DHA plasma levels , assessing unadjusted impact , impacts adjusted for one another , and fully adjusted for comorbidities , EPA + DHA , and the EPA / DHA ratio on 10-year Major Adverse Cardiovascular Events ( MACE ). Higher EPA but not DHA were associated with a lower risk of MACE , and when combined with EPA , higher DHA appeared to blunt the benefit of EPA . Of most concern , DHA was associated with a higher risk of MACE in the presence of low EPA .
These findings may further elucidate conflicting outcomes from LCPUFA supplementation .
Surprisingly , some studies also show DHA supplementation to be deleterious for cognition when compared to a placebo in healthy developed human brains . ( 29 , 30 ) Research estimates that only 2.4-3.8 mg / day is required to maintain a healthy , developed human brain , while supplementation typically occurs at far higher amounts .( 19 ) It is often believed that a higher intake of any given natural substance must be beneficial , though common sense , and research , challenges this - even lower dose refined Buglossoides arvensis seed oil outperformed higher dose Buglossoides arvensis , and yet performed just as well as the same dose of fish oil in a rheumatoid arthritis animal-model clinical trial .( 31 ) Studies in non-fish eating populations have suggested a negative feedback inhibition mechanism from preformed DHA intake , which has now been confirmed by research , and may be one factor in the varied outcomes from preformed DHA intakes .( 9 , 10 ) Additionally , though controversially , the triacylglycerol ( TAG ) -DHA found in most supplemental forms may be unable to cross the blood-brain barrier , in contrast to lysophosphatidylcholine ( LPC ) -DHA which is the form biosynthesised in the liver from ALA - this suggests that the rise we see in blood levels following supplementation with TAG-DHA could conversely be an indicator that the body is not utilising this DHA in the tissues in which it is best situated .( 32 )
Omega 3 ALA & SDA - the omegas of emerging consequence
Choosing an omega-3 source that provides ample ALA and SDA may readily elevate plasma EPA levels and meet tissue DHA requirements , while respecting the body ’ s natural metabolism pathway . ALA is known to hold cardioprotective benefits and in the NHANES study only serum ALA correlated to lower cancer death risk ( not LA , EPA , or DHA ).( 28 , 33 , 34 )
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