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Nutra Report
Vegetarian Docosahexaenoic acid (DHA) and Triglyceride Reduction
GENERAL INFORMATION:
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Active component[s]: DHA.
Source material: Marine algae.
Dosage route: Oral.
Directions of use and/or Duration of use: A clinical
literature search did not yield specific results pertaining
to directions of use and/or duration of use.
Target Population: Infants, children, adults.
Risk Information:
 The following have been reported with DHA intake: gastrointestinal upset, belching,
loose stools, dry mouth, fishy aftertaste, decreased libido, dizziness, headache,
insomnia, anxiety, increased cholesterol, decreased blood glucose.
 Patients with allergy to fish, fish oil or marine products should use caution.
 Based on potential interactions, consult a health care practitioner prior to use if you are
pregnant or breastfeeding, or if you are taking blood thinners, lipid lowering agents,
blood pressure lowering agents and/or blood sugar lowering agents.
HUMAN HEALTH INDICATIONS:
Recommended Use or Purpose
General
Helps to lower levels of blood triglycerides.
Adults
0.7-3 g per day
(Conquer, 1996; Kelley, 2007; Maki, 2005; Neff, 2010; Stark, 2004;
Theobald, 2004)
DHA
Docosahexaenoic acid [DHA; 22:6n-3] is a long-chain polyunsaturated omega-3 fatty acid. DHA has 22
carbons with six double bonds and is in the omega-3 family of polyunsaturated fatty acids. The omega-3
fatty acid family includes the essential fatty acid alpha-linolenic acid [18:3n-3], found in plant foods such
as flax, soy and walnuts, as well as eicosapentaenoic acid [EPA] [20:5n-3], found in fish and marine oils.
All fatty acids in this family have their first double bond three carbons from the methyl end. In North
America, the recommended intake of alpha-linolenic acid is 1.1 g [females] and 1.6 g [males] (Food and
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Nutrition Board, 2005). There is no specific recommendation for DHA, although The American Heart
Association recommends 1000 mg EPA+DHA daily for individuals with cardiovascular disease [or 2-4 g
daily for individuals with high levels of blood triglycerides] (Kris-Etherton, 2002) and general
recommendations include increasing intake of pre-formed long-chain EPA plus DHA and/or intakes of EPA
plus DHA at levels of approximately 10% of the total intake of omega-3 fatty acids (Food and Nutrition
Board, 2005). Although DHA can be synthesized from alpha-linolenic acid, the conversion is low (Burdge,
2002a; Burdge, 2002b; Innis, 1994; Plourde, 2007).
DHA is commonly found in fish and other marine foods, and is an important fatty acid in fish oil and
omega-3 fatty acid supplements. However, vegetarian-source DHA can be isolated from marine algae. It
has been shown that DHA from algal oil is bioequivalent to cooked salmon in providing DHA to plasma
and red blood cells (Arterburn et al., 2008). Alternate sources of DHA are of interest to non-fish eaters
[including vegetarians], populations in which increased EPA may be of concern [e.g. infants] and for those
concerned with the potential decrease of fish stocks (Kyle, 1998; Sargent, 1999). Omega-3 fatty acids,
including vegetarian DHA, have been incorporated or enriched in various foods and beverages in an effort
to increase intake of these fatty acids (Arterburn et al., 2007; Lewis, 2000; Riediger, 2009). Many infant
formulas on the market in North America contain 0.3-0.35% of fat as DHA, usually sourced from vegetarian
algal oil.
In the body, DHA is found in all cell membranes and plasma phospholipids, but is highest in the fluid
membranes in the brain, retina and spermatozoa. Health benefits possibly associated with DHA include
cardiovascular health, due to its presence in fish oil, as well as cognitive and neuropsychiatric health and
male infertility, due to its presence in cell membranes in the body.
DHA AND TRIGLYCERIDE LOWERING
Various studies have investigated the effect of DHA on cardiovascular disease risk factors. Most studies
were conducted in healthy individuals although some have studied hypertriglyceridemic patients. Algal
DHA has been shown to reduce triglyceride levels in many studies (Conquer, 1996; Davidson, 1997;
Geppert, 2006; Kelley, 2007; Maki, 2005; Neff, 2010; Stark, 2004). As commonly observed in fish oil
studies, DHA may also increase total and LDL cholesterol (Davidson, 1997; Geppert, 2006; Kelley, 2007;
Maki, 2005), however, this appears to be associated with a decrease in small dense LDL cholesterol [i.e.,
the more atherogenic sub-type of cholesterol] and an increase in the large, buoyant, less atherogenic subtype (Engler, 2005; Kelley, 2007; Maki, 2005; Neff, 2010; Theobald, 2004;) and an increase in HDL
cholesterol (Conquer, 1996; Davidson, 1997; Geppert, 2006; Stark, 2004). Other risk factors that may be
benefited by algal DHA intake include decreased heart rate (Stark, 2004). The mechanism by which DHA
decreases triglyceride levels is not clear. Possibilities include increased lipoprotein lipase activity (Park,
2004; Park, 2003).
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DHA AND COGNITIVE HEALTH
It is well known that DHA undergoes rapid accretion in the brain during prenatal development and during
the first postnatal year. Early studies in breastfed infants, a source of dietary DHA, found higher levels of
DHA in the infant brain vs. formula fed [lacking DHA] infants. Given the importance of DHA for the
developing infant, especially the premature infant, most, recent studies have investigated the effect of
DHA in combination with arachidonic acid [AA, 20:4n-6]. Based on many reviews in the field, most authors
are in support of addition of both DHA and AA to term and pre-term formula (Cheatham, 2006; Fleith,
2005; Heird, 2005; Wright, 2006). Based on a meta-analysis of 12 studies, DHA-supplemented formula
increased visual acuity at four months in term infants (SanGiovanni, 2000). Fortification of formula with
DHA also prevents the decline of blood DHA levels observed in infants fed formula lacking DHA (Clandinin,
1997; Smit, 2000).
DHA has also been studied for its cognitive benefits in healthy individuals and in individuals with dementia.
DHA is thought to play a role in amyloid-beta peptide signalling in Alzheimer's disease (Lukiw, 2009),
perhaps following conversion to its metabolite neuroprotectin D1 (Lukiw, 2008). In persons with
Alzheimer’s disease, levels of neuroprotectin D1 may be decreased in the hippocampal region (Lukiw,
2005). Although based on epidemiological study, DHA intakes are inversely correlated with dementia risk
(Johnson, 2006; Schaefer, 2006) and patients with Alzheimer’s disease have been shown to have
decreased DHA status (Conquer, 2000a), the effect of algal DHA in dementia or Alzheimer’s disease has
not been studied extensively. The source of DHA was not indicated in a study by Terano in which mini
mental state examination [MMSE] scores increased following six months of DHA use (Terano, 1999). In a
study using algal DHA, however, a lack of benefit was observed in Alzheimer’s patients (Quinn, 2010).
SAFETY AND TOXICITY:
DHA has been safely administered in human clinical research at dosages of up to 4 g daily for up to 15
weeks in adults. DHA is commonly added to marketed infant formulas at levels of approximately 0.3% fat.
Common adverse effects include increased total cholesterol or LDL cholesterol, suggesting caution in
patients with increased cholesterol levels (Davidson, 1997; Kelley, 2007; Geppert, 2006; Maki, 2005). Also,
some evidence suggests an association of omega-3 intake [including DHA] with increased levels of fasting
glucose, suggesting caution in patients with diabetes or those using hypoglycemic agents (Woodman,
2002).
Based on clinical trials, adverse effects to DHA supplementation are generally mild. Examples include
gastrointestinal upset [gas, bloating], belching, loose stools, dry mouth, and fishy aftertaste (Kelley, 2007;
Marangell, 2003; Mischoulon, 2008). In patients with depression, adverse effects include decreased libido,
dizziness, headache, insomnia and anxiety (Marangell, 2003; Mischoulon, 2008).
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Animal and/or in vitro/ex vivo toxicity literature indicates a lack of safety concern regarding algal DHA
(Blum, 2007a; Blum, 2007b; Hadley, 2010; Hammond, 2002; Kroes, 2003; Lein, 2009). The no-adverseeffect level [NOAEL] in rats for DHASCO oil [algal DHA] was the highest dose level [1.25 g per kg per day]
(Arterburn, 2000).
CAUTIONS, WARNINGS, CONTRAINDICATIONS AND INTERACTIONS
Consult a health care practitioner prior to use if you have a pre-existing medical condition, are taking
prescription medication, or are pregnant or breastfeeding.
For additional information from the clinical literature regarding interactions, please refer to the following
tables:
DRUG
INTERACTION WITH DHA
Anticoagulants and
Antiplatelets
Blood Pressure Lowering
Agents
DHA ethyl ester resulted in a decrease in collagen-induced platelet
aggregation and thromboxane A2 levels (Woodman, 2003). However,
DHA had no effect on blood coagulation, platelet function, or thrombotic
tendencies (Nelson, 1997). Thus, DHA may interfere with medications
[heparin, warfarin or clopidogrel] or natural health products [Ginkgo
biloba, saw palmetto or garlic] that increase the risk of bleeding.
DHA-rich oils have been shown to lower blood pressure (Kimura, 2002;
Mori, 1999). Effect of algal DHA is unclear.
Blood Sugar
Omega-3 fatty acids may increase blood sugar and potentially exert
additive effects with medications, herbs and dietary supplements that
have hypoglycaemic properties. The effect of algal DHA is unclear.
Carbamazepine
Patients on carbamazepine had lower DHA levels (Yuen, 2008).
Hormones
DHA levels were higher in patients not using oral contraceptives (Giltay,
2004) and in those using hormone replacements (Stark, 2004).
Lipid-Lowering Drugs
DHA has been shown to decrease levels of blood triglycerides and
increase levels of total, LDL and HDL cholesterol (Conquer, 1996; Kelley,
2007; Maki, 2005, Stark, 2004).
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NATURAL HEALTH PRODUCTS INTERACTION WITH DHA
[NHP] SUBSTANCES
Eicosapentaenoic Acid
[EPA]
Supplementation with EPA alone [in the absence of DHA] can potentially
result in a reduction in red blood cell DHA (Higashihara, 2008).
Vitamin E
DHA supplementation for four years may decrease vitamin E levels
(Wheaton, 2003).
FOOD
INTERACTION WITH DHA
Medium Chain
Triglyceride Formula
Use of an infant formula containing high levels of medium chain
triglycerides may decrease plasma DHA (Carnielli, 1996).
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