Many nutritional supplements come in an array of competing forms, and their marketers strive to convince consumers that their product offers superior absorption or efficacy.
The long list of controversies includes chromium (picolinate vs. polynicotinate), OPCs (grape seed vs. pine bark), vitamin C (ascorbic acid vs. Ester C®), calcium (carbonate vs. citrate), ginseng (Asian vs. American) and echinacea (E. purpurea vs. E. angustifolia).
It’s almost enough to make one swear off supplements.
But in most cases, reasonably clear answers to questions about relative absorption and efficacy of different supplement forms are available … if you track down and decipher the scientific papers.
What about omega-3s?
We explained the several important distinctions between plant-source and marine omega-3s in a recent issue (see "Beware the Omega-3 Bait-and-Switch”), but there are also distinctions among fish oil supplements.
Fish oil supplements: the distillation distinction
Omega-3s from fish oil (EPA and DHA) come to consumers attached to one of two kinds of molecules—triglyceride esters or ethyl esters.
Omega-3 triglycerides are esters formed from the joining of glycerol to three omega-3 fatty acids.
The ethyl ester form of omega-3s found in about 10 percent of refined fish oils results when EPA and DHA are extracted from their natural glycerol structure by means of "trans-esterification” with ethanol.
For convenience, we’ll refer to triglyceride and ethyl ester "forms” of omega-3s, but it is more accurate to think of them as two different omega-3 "packages”.
The body recognizes both forms (triglyceride or ethyl ester) of fish-derived omega-3s, and it uses enzymes to switch omega-3s from either package to another as needed to serve different metabolic functions.
Almost all of the long-chain omega-3-fatty acids (EPA and DHA) in fish — and in all Vital Choice fish oils — occur in the triglyceride form.
In contrast, about 10 percent of refined fish oil supplements—except our refined High-Potency pollock oil—contain the ethyl ester form of omega-3s.
This is because nearly all fish oil supplement makers—for reasons that will become clear—put their oil through a process called molecular distillation (or, less commonly, supercritical carbon dioxide extraction).
The chief purpose of molecular distillation is to remove the minuscule traces of industrial contaminants (e.g., heavy metals, dioxins and PCBs) present in fish oils, and/or to concentrate the "star" omega-3 molecules, EPA and DHA.
How does molecular distillation work?
Molecular distillation removes omega-3-fatty acid molecules, intact, from their natural glycerol companion molecule via a process called re-esterification, and can then place the omega-3s in an ethyl ester or keep them in a triglyceride package.
In most cases, molecular distillation involves flash-heating the oil to high temperatures (about 460° Fahrenheit; 260° centigrade) in the presence of a vacuum.
Some call ethyl ester omega-3s synthetic, but this is not accurate. The human body also re-esterifies fatty acids as needed to suit various purposes.
What is a part per trillion?
A little perspective is in order... one part per trillion is a million times less than one part per million. Or look at at this way:
A single teaspoon of salt in Lake Superior would equal a few parts per trillion. It’s hard to imagine anything being hazardous in such vanishingly small amounts.
(Note: Most supplemental fish oil is produced using a modified distillation processes that yields triglyceride-bound omega-3s.)
Does this distinction between the chemical packages in which omega-3s can be consumed produce meaningful physiological differences? It appears so.
A literature search on PubMed—the world’s largest biomedical database—reveals only five clinical studies designed to determine which form is better absorbed by the human body.
In each case, the investigators gauged absorption rates by looking at the blood levels of EPA and DHA that result from ingesting the two divergent forms of marine omega-3s: the ethyl ester form in about 10 percent of supplemental fish oils, and the triglyceride form that occurs naturally in fish and in all Vital Choice fish oil capsules.
Natural fish oils exhibit absorption edge in four head-to-head trials
Results were mixed among the four clinical studies that compared the two forms of supplemental omega-3s, but the natural form came out ahead, overall:
- Two studies produced neutral results, with the two forms of omega-3s absorbed equally well.
- Two studies showed that triglyceride omega-3s produce substantially higher blood levels of omega-3s.
The contributors to a Wikipedia encyclopedia entry on omega-3s came to the same conclusion regarding the available evidence:
"Of the four studies that compare bioavailability of the triglyceride form of fish oil vs. the ester form, two have concluded that the natural triglyceride form is better, and the other two studies did not find a significant difference. No studies as yet have shown the ester form to be superior although it is cheaper to manufacture.”
Why should studies comparing rates of omega-3 absorption from ethyl ester and triglyceride type supplements produce different results?
At least in part, the answer may lie in the dietary context—high-fat or low-fat—accompanying supplemental doses of omega-3s.
Standard supplements need fatty food
The makers of concentrated omega-3 supplements often tout the artificially high concentrations of omega-3s (EPA and DHA) as a benefit of their distilled fish oils.
However, the results of one of the trials mentioned above—an intriguing investigation in Utah—suggest that the full range of fats in wild salmon enhance absorption of omega-3s.
The Utah team performed two studies intended to compare the absorption of ethyl ester omega-3s and natural triglyceride omega-3s.
The first study showed much higher absorption of natural triglyceride omega-3s, while the second showed that the ethyl ester omega-3s in distilled fish oils were poorly absorbed unless taken with a high-fat meal.
The authors came to this conclusion: "Absorption of both EPA and DHA from fish oil ethyl esters was increased three-fold [i.e., by 300 percent], to about 60%, by co-ingestion with the high-fat meal indicating that absorption of fatty acid ethyl esters is highly dependent on the amount of co-ingested fat."
Put another way, only 20 percent of the omega-3s in the standard, ethyl ester form were absorbed, unless they were taken with a high-fat meal, which raised the absorption level three-fold, to 60 percent… at the cost of having to ingest an extra 324 dietary calories: 72 calories in the low-fat meal versus 396 calories in the high-fat meal.
In contrast, the absorption of both fish-derived omega-3s (EPA and DHA) in their natural triglyceride form was substantially greater in either context (high-fat or low-fat): absorption of DHA was equally superior with either low-fat meals or high-fat meals, while participants' absorption of EPA increased from an already-high 69 percent to 90 percent when taken with a high-fat meal.
In other words, fish oils whose omega-3s occur in the ethyl ester form result in much less absorbed omega-3 unless consumers take the capsules with a fat from foods.
Absorption study # 5: Whole salmon beats standard supplements
Perhaps the most interesting and significant study on this subject (Visioli F, et al, 2003) compared absorption of omega-3s from salmon—that is, in the triglyceride form—with absorption of ethyl ester omega-3s from distilled fish oil supplements.
Daily for six weeks, volunteers recruited by researchers at Italy’s University of Milan consumed roughly equivalent doses of omega-3s from one of two sources:
- Salmon (three ounces) containing 383 mg of EPA and 544 mg of DHA
Distilled fish oil containing 450 mg of EPA and 318 mg of DHA in the ethyl ester form (taken either in one dose or three equally divided doses).
The team also reevaluated data from a previous study carried out with the same design, using fish oil capsules that delivered much higher doses of omega-3s (2,580 mg per day of EPA and 1,920 mg of DHA).
The results were clear, and favored salmon as a source of well-absorbed omega-3s.
As the Italian team said: "We provide experimental evidence that omega-3 fatty acids from fish are more effectively incorporated into plasma lipids than when administered as capsules ... increments in plasma EPA and DHA concentration [i.e., omega-3 blood levels] after salmon intake were significantly higher than after administration of [fish oil] capsules. The same increments would be obtained with at least two- and nine-fold higher doses of EPA and DHA, respectively, if administered with capsules rather than salmon.”
The presence of other factors in salmon (such as the various carotenoids and fatty acids) might be responsible for the large absorption advantage recorded in Milan.
That’s a question for other researchers to tackle. In the meantime, it’s reassuring to know that the balance of evidence indicates an absorption advantage for omega-3s in the "natural” triglyceride form found in all Vital Choice fish oils.
What about safety?
Conventional wisdom holds that molecular distillation of fish oils is the benchmark for safety, with seemingly no consideration given to its impact on the oil’s nutritional value or efficacy.
While contaminants are a legitimate concern, the evidence sited above indicates that molecular distillation exacts its own deleterious toll on the oil in exchange for the elimination of hazardous levels of contaminants.
The key words here are "hazardous levels.” Modern technology is capable of identifying truly minuscule amounts of these substances—a few parts per trillion.
Cautious regulators set safety levels that include extremely large safety margins.
For instance, the U.S. Environmental Protection Agency (EPA) "maximum safe level” for PCBs—0.02 ppb per kg (2.2 lbs.) of body weight per day—is 300 times lower than the lowest dose at which subtle health effects have been seen in the offspring of laboratory monkeys fed PCBs.
And the daily intake guideline for PCBs set by Health Canada (their equivalent to the U.S. FDA)—1ppb per kg (2.2 lbs.) of body weight per day—is 50 times greater than the U.S. EPA’s limit.
- Lawson LD, Hughes BG. Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Commun. 1988 Oct 31;156(2):960-3.
- Lawson LD, Hughes BG. Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Commun. 1988 Apr 15;152(1):328-35.
- Beckermann B, Beneke M, Seitz I. [Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers] Arzneimittelforschung. 1990 Jun;40(6):700-4. German.
- Yang LY, Kuksis A, Myher JJ., 1990. Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination. J Lipid Res. 1990 Jan;31(1):137-47
- Visioli F, Rise P, Barassi MC, Marangoni F, Galli C. Dietary intake of fish vs. formulations leads to higher plasma concentrations of n-3 fatty acids. Lipids. 2003 Apr;38(4):415-8.
- Krokan HE, Bjerve KS, Mork E. The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta. 1993 May 20;1168(1):59-67.
- Nordoy A, Barstad L, Connor WE, Hatcher L. Absorption of the n-3 eicosapentaenoic and docosahexaenoic acids as ethyl esters and triglycerides by humans. Am J Clin Nutr. 1991 May;53(5):1185-90.
- el Boustani S, Colette C, Monnier L, Descomps B, Crastes de Paulet A, Mendy F. Enteral absorption in man of eicosapentaenoic acid in different chemical forms. Lipids. 1987 Oct;22(10):711-4.
- Omega-3 fatty acid. From Wikipedia, the free encyclopedia. Accessed online September 3, 2005 at http://en.wikipedia.org/wiki/Omega-3_fatty_acid.