T Nation

Omega 3's Are Bad For You?


#1

An article some may find interesting. Apparantly there is some backlash against Omega 3's brewing. I'm not saying I'm in agreement with it, but I was hoping it may create some healthy debate.

OMEGA 3 PUFAs ARE EVEN MORE DAMAGING
THAN OMEGA 6 PUFAs.

 EPA, DHA, and ALA are far more subject to oxidative damage than are the omega 6 fatty acids. Fish oils not only rapidly destroy vitamin E in the body, but they spontaneously oxidize with incredible speed, even before they reach the bloodstream. In undergoing such rapid oxidation, they form strange and ultra-pathological fatty acids, much as omega 6 fatty acids do in response to heat.

That is why even though the short-term anti-prostaglandin effects of omega 3 oils are shown in the literature to benefit many diseases, the long-term peroxidative effects specifically cause damage to the brain, liver, skin, thymus, spleen, and heart, and accelerate the progression of diseases such as atherosclerosis, stroke, diabetes, and cancer.

 The first place where PUFA peroxidative damage was studied was in regard to lipofuscin age pigment. Interestingly, it was found that as this pigment formed in the skin, it simultaneously formed in the brain. In other words ...

A MAN WITH AGE SPOTS ON HIS SKIN HAS
AGE SPOTS ON HIS BRAIN TO THE SAME DEGREE.

 There is much more to be said about ...

THE DAMAGING EFFECTS OF OMEGA 3 OILS
ON THE BRAIN.

 EPA and DHA form isoprostanes and neuro-prostanes during their lipid peroxidation. These substances behave in many ways like the damaging prostaglandins and leukotrienes. The brain is particularly sensitive to oxidative damage and excitatory toxicity from these omega 3 derivatives. Research shows that EPA and DHA cause brain swelling and increased cerebral blood vessel permeability.

When DHA is added to cultured cells from the cerebral cortex, they produce free radicals, and stimulate the production of both malondialdehyde and lactate. The malondialdehyde shows dysaerobic catabolic damage to the brain, and lactate shows anabolic/anaerobic damage to the brain. Furthermore, the DHA inhibits the uptake of glutamic acid, which allows for prolonged excitation of the nerve cells.

 In a comparison between DHA and other PUFAs with saturated fatty acids, the PUFAs cause the production of free radicals and swelling of the brain, while the saturated fats did not. PUFAs inhibit the respiration of mitochondria in brain cells while producing edema, while saturated fatty acids cause no problems.

Free radical activity is shown to cause the liberation of free fatty acids from the cellular structure, as well as activation of lipases associated with the loss of potassium from the cells --- another indication of dysaerobic cellular damage. The prolonged neuro-excitation caused by PUFAs becomes a self stimulating process leading to cellular destruction.

J Neuro Chem. 1980 Oct;35(4):1004-7. Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling. Chan, et al.

Brain Res. 1982 Sep 23;248(1):151-7. Alterations of membrane integrity and cellular constituents by arachadonic acid in neuro blastoma and glioma cells. Chan, et al.

J Neuro Chem. 1982 Feb;38(2):525-31. Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices. Chan, et al.

J Neurosci Res. 1984; 12(4):595-605. Release of polyunsaturated fatty acids from phospholipids and alteration of brain membrane integrity by oxygen-derived free radicals. Chan, et al.

J Neurochem. 1988 Apr;50(4):1185-93. Induction of intracellular superoxide radical formation by arachadonic acid and by polyunsaturated fatty acids in primary astrocytic cultures. Chan, et al.

J Neurosci Res. 1988 Aug;20(4):451-6. Role of arachadonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia. Hillered, et al.

J Neurosci Res. 1989 Oct;24(2):247-50. Brain mitochondrial swelling induced by arachadonic acid and other long chained free fatty acids. Hillered, et al.

J Physiol. Feb 15;475(1):83-93. Facilitatory effect of DHA on N-methyl-d-aspartate response in pyramidal neurons of rats? cerebral cortex. Nishikawa, et al.

Neuro Chem Res. 1994 Jan;19(1):57-63. Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line. Ray, et al.

Free Radic Biol Med. 2000 Oct 15;29(8):714-20. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamine uptake in primary neuronal cultures. Lovell, et al.

 Polyunsatureated fats impair fetal and infant brain development (while saturated fats are essential for normal brain development and nerve myelination).

Martin et al. Journal Of Nutrition 125(4), 1017-1024, 1995.

 Dietary polyunsaturated fats suppress the activity of endogenous omega-9 unsaturated fats, which researchers suspect may be the trophic substance of greatest importance both to the brain and to the immune system.

Cleland, et al. ?Effect Of Dietary N-9 Eicosatrienoic Acid On The Fatty Acid Composition of Plasma Lipid Fractions And Tissue Phospolipids.? Lipids, 1996 Aug, 31:8, 829-37.

 Combining what you just learned about the damage to the brain by omega 3 PUFAs with what you already know (from previous Letters) about the essentiality of saturated fat for brain development in infancy -- ask yourself how you feel about ...

THE AGRI-BUSINESS PUSH
TO PUT DHA IN BABY FORMULA,
AND FISH OIL IN SCHOOL LUNCHES.

--- Ah, but the omega 3 ? infant connection does not end there. Among the many benefits of nursing infants for the first few months of life is the decreased incidence of allergic sensitivity. However, it has been shown that in mothers who consume high quantities of omega 3 fatty acids, their infants are at increased risk of developing allergies.

Clin Exp Allergy. 2004 Feb;34(2):194-200. Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breast fed infants. Stoney, et al.

 Also related to omega 3 oils and brain function:

 A significant portion of the advertising hype regarding fish oil supplementation is its purported beneficial effect on depression, psychosis, and dementia. Contrary to the propaganda, a legitimate scientific study of over 29,000 male subjects reported that the use of omega 3 oil or consumption of fish had no beneficial effect on depression, and furthermore did not decrease the incidence of suicide in the least.

Am J Psychiatry. 2004 Mar;161(3):567-9. Is low dietary intake of omega 3 fatty acids associated with depression? Hakkarainen, et al.

 You clearly see the potential harm done by EPA, DHA, and ALA supplementation. Since, until recently, our intake of omega 3 oils was miniscule compared to our omega 6 consumption, fish oil and flax oil damage was rarely significant. But now, with countless thousands being snookered by Agri-business propaganda, we have a problem that only well-informed clinicians like yourself can solve.

We have not yet even discussed (wait til next month?s Letter) the immuno-suppressive and cancer-causing effects of omega 3 PUFAs, nor the damage they do to the cardiovascular system; yet you should already feel a sense of urgency to spread the truth. Please --- inform your patients, and, protect them from oxidative stress with OXY POWER.

Sincerely,
Guy Schenker, D.C.

"Edited for length"

http://www.nutri-spec.net/nl/2006-01.html


#2

Cy Willson should drop by and de-bunk this any moment now....


#3

http://www.chirobase.org/06DD/nutrispec.html

NUTRI-SPEC Testing Is Pseudoscientific Nonsense
Stephen Barrett, M.D.

NUTRI-SPEC Testing is claimed to enable the practitioner to quickly determine the specific nutrition needs of individual patients. The testing system was developed by Guy R. Schenker, D.C., of Mifflintown, Pennsylvania, and has been marketed with messages like:

How can you rise straight to the top of the clinical nutrition field? With a scientific testing system to determine the specific nutritional needs of every patient in your own office in five minutes; and the supplements to fulfill those needs immediately - with NUTRI-SPEC. . . .Your patients will fully appreciate your professionalism as you scientifically uncover the causes underlying their health problems, instead of taking a shot in the dark at their symptoms [1].

Interested chiropractors can purchase a 372-page manual and can borrow or purchase a videotape showing how the system is used with seven patients. According to the book:

* There is no patient whose health problem does not have a nutritional component. . . . That makes nutrition a clinical tool with universal application and with almost unlimited potential.
* Every condition or disease can be defined in terms of its Pattern of Biochemical Imbalance and/or its Patter of Endocrine Dysfunction [2.]

Brochures for patients assure that NUTRI-SPEC tests tell the chiropractor "in what ways your body chemistry tends to slip off balance" and reveal "exactly which foods and nutritional supplements you need and which you should avoid." [3]

During the first visit, the chiropractor determines the patient's respiratory rate, body temperature, blood pressure, pulse (standing or lying down), breath-holding ability, pupil size, degree of thickness or coating of the tongue, several characteristics of the patient's saliva and urine, and various reflexes.

Saliva and urine samples can also be sent together with other data to obtain a " NUTRI-SPEC PROFILE" that provides additional information. Using NUTRI-SPEC's unique scoring system, the chiropractor then determines whether the patient is in or out of "water/electrolyte balance," "anaerobic/dysaerobic balance," "acid/alkaline balance," and "sympathetic/parasympathetic balance." The test findings also enable the chiropractor to diagnose "sex hormone insufficiency," "myocardial insufficiency," "pineal stress," "thymus stress," and about twenty-five other fanciful conditions.

Based on all these findings, the chiropractor makes dietary recommendations and prescribes supplements (available only from NUTRI-SPEC) to correct the alleged imbalances. The supplements would cost patients like those shown in the video from 80? to about $3 per day, half of which is profit to the chiropractor. If follow-up visits -- "repeating just the tests that were abnormal"-- fail to show "improvement," the dosage of these products is adjusted.

Simply put, NUTRI-SPEC is pseudoscientific nonsense. If you encounter a practitioner who uses it, please ask your state attorney general to investigate.

References

  1. Advertisements, Digest of Chiropractic Economics, 1990-1991.
  2. Schenker GR. An Analytic System of Clinical Nutrition, pp 1-3. Self-published, 1989.
  3. The secret of good nutrition. Undated, distributed in 1991.

#4

http://www.quackwatch.org/01QuackeryRelatedTopics/chirochoose.html

Tips on Choosing a Chiropractor
Stephen Barrett, M.D.

Choosing a chiropractor can be difficult because the majority of chiropractors are involved in unscientific practices [1,2]. If you do decide to consult one, begin with a telephone interview during which you explore the chiropractor's attitudes and practice patterns.
Positive Signs

Try to find a chiropractor whose practice is limited to conservative treatment of back pain and other musculoskeletal problems. Ask your medical doctor for the names of any who fit this description and appear to be trustworthy.

Membership in the National Association for Chiropractic Medicine or the Canadian Academy of Manipulative Therapists (CAMT) is a very good sign, but the number of chiropractors who belong to these groups is small. CAMT's "orthopractic guidelines" describe a science-based approach to manipulative therapy.

In addition to manual manipulation or stretching of tight muscles or joints, science-based chiropractors commonly use heat or ice packs, ultrasound treatment, and other modalities similar to those of physical therapists. They may also recommend a home exercise program. For most conditions that chiropractic care can help, significant improvement should occur within a few visits.
Negative Signs

Avoid chiropractors who advertise about "danger signals that indicate the need for chiropractic care," make claims about curing diseases, try to get patients to sign contracts for lengthy treatment, promote regular "preventive" adjustments, use scare tactics, or disparage scientific medical treatment or preventive measures such as immunization or fluoridation.

Avoid chiropractors who purport to diagnose or treat "subluxations," who have waiting room literature promoting "nerve interference" as an underlying cause of disease, or who post charts or distribute literature suggesting that chiropractic might help nearly every type of health problem.

Avoid any chiropractor who routinely performs or orders x-ray examinations of all patients. Most patients who consult a chiropractor do not need them. Be especially wary of full-spine x-ray examinations. This practice has doubtful diagnostic value and involves a large amount of radiation.

Avoid chiropractors who "prescribe" dietary supplements, homeopathic products, or herbal products for the treatment of disease or who sell any of these products in their offices. For dietary advice, the best sources are physicians and registered dietitians.

Avoid chiropractors who offer Biological Terrain Assessment, body fat analysis, computerized "nutrient deficiency" testing, contact reflex analysis,, computerized range-of-motion analysis, contour analysis (also called moire contourography), cytotoxic testing, electrodermal testing, Functional Intracellular Analysis (FIA), hair analysis, herbal crystallization analysis, inclinometry, iridology, leg-length testing, live blood cell analysis (also called nutritional blood analysis or Hemaview), testing with a Nervo-Scope or similar spinal heat-detecting device, Nutrabalance, NUTRI-SPEC, pendulum divination, reflexology, saliva testing, spinal ultrasound testing to "measure progress, surface electromyography (SEMG), thermography, a Toftness device, weighing on a twin-scale device called a Spinal Analysis Machine (S.A.M.), or any other dubious diagnostic procedure identified on Quackwatch.

Avoid chiropractors who utilize acupuncture, Activator Methods, allergy testing, applied kinesiology, Bio Energetic Synchronization Technique (B.E.S.T.), chelation therapy, colonic irrigation, cranial or craniosacral therapy, laser acupuncture, magnetic or biomagnetic therapy, Neuro Emotional Technique (NET), or Neural Organization Technique (NOT), or who exhibit a dogmatic attachment to any other specific chiropractic technique or school of thought.

Understand that some chiropractic treatments involve significant risk. Spinal manipulations involving sudden movements have greater potential for injury than more conservative types of therapy. Be aware that chiropractic neck manipulation can cause serious injuries. Neck manipulation should be done gently with care to avoid excessive rotation that could damage the patient's vertebral artery. It should never be used unless symptoms indicate a specific need for it. A small percentage of chiropractors advocate neck manipulation to "balance" or "realign" the spine no matter where the patient's problem is located. I recommend avoiding such chiropractors.
Additional Safeguards

Never consult a chiropractor unless your problem has been diagnosed by a competent medical practitioner. Don't rely on a chiropractor for diagnosis. Although some chiropractors know enough to avoid diagnostic difficulty, there is no simple way for a consumer to determine who can do so. As an additional safeguard, ask any chiropractor who treats you to discuss your care with your medical doctor.

Remember that although manipulative therapy has value in treating back pain and may relieve other musculoskeletal conditions, chiropractors are not the only source of manipulative therapy. Physical therapists, many osteopathic physicians, and a small number of medical doctors do it also. The Canadian Association of Manipulative Therapists is a good referral source for Canadian practitioners.
References

  1. Christenson MG, Morgan DRD. Job Analysis of Chiropractic: A Report, Survey Analysis, and Summary of the Practice of Chiropractic within the United States. Greeley, Colorado: National Board of Chiropractic Examiners, 1993. This report is based on the responses by 4,835 full-time chiropractors who responded to a 1991 NBCE survey about their practices during the previous two years. The figures included: Activator Methods 51.2%, applied kinesiology 37.2%, acupressure/meridian therapy 65.5%, acupuncture 11.8%, cranial adjusting 27.2%, and homeopathic remedies 36.9%. "Nutritional counseling, etc." was listed by 83.5%. Although the data don't indicate what this involved, it is clear that a large percentage are inappropriately prescribing dietary supplements.
  2. Chiropractors. Consumer Reports 59:383-390, 1994. This included a survey of 476 chiropractors chosen randomly from the American Chiropractic Association membership directory. Nearly one quarter of the 274 who responded sent material stating that spinal misalignments and "interferences" threatened overall health, and 35% implicated the spine in disorders of the body's organs.

#5

"Healthy Debate!" Get it? Healthy.... What?

-Fireplug


#6

what the heck is this bs


#7

wow i just check out that nutri spec website, what a load of garbage


#8

http://www.nutri-spec.net/anabolicergogenic.htm

Niiiice


#9

It's too bad Arnold didn't have Nutri-Spec when he was competing. He might have gotten huge!


#10

HA, next your going to tell me that Iraq didn't have nuclear weapons and that Iran was the real threat all along. Oh wait, what I said is actually true.

Omega-3s are good for you, TC says so.


#11

What happened to a discussion about the merits of fish oil? Why are we disussing chiro's instead of the content of the alleged studies???


#12

It actually sounds pretty bogus.

Without going and searching, even the titles of the studies seem to hint that this is not quite on par.

The titles suggest that they are not in fact researching the issues discussed, and the dates would indicate that this certainly should not be "new" information that nobody was aware of until now.

Considering the final sentence of the "report" I find the whole thing very suspect indeed. Sure, let's all go buy oxy-free or whatever it's called, that is the solution to all these concerns.

However, the real piss off is that if this is misinformation in an attempt to sell a specific product, it is very inappropriate to lead people away from products that are beneficial to normal bodily functions.

Just yesterday I was reading some literature over at the Life Extension Foundation about how omega-3's are able to halt certain liver cancers and they help cells undergo apoptosis, which means they die as they should instead of proliferating wildly. Research is ongoing.

Honestly, I'd suspect that drug companies are going out and finding ways to fight against natural foods and supplements, in order to make sure that their products don't have serious competition.


#13

Did anybody look at that long list of references? A lot of the references were in regards to polyunsaturated fats in general and didn't even mention omega-3s.


#14

Because the people saying Omega 3s are bad in this article make their money by promoting pseudo-science through chirpractors?


#15

This guy is a chiro-quacker.


#16

the first thing I saw in bold when I clicked one of the links was "Most Food intake should come from saturated fat" I laughed hard. I proceded to close the window, and started reading the Biotest supplement articles, as to not piss of the t-gods.


#17

I was originally going to provide just the references and let people decide for themselves what they thought, as to limit people's biases and knee jerk reactions.

I guess I should have explained the context of the article ahead of time as to not cause any confusion. It's a newsletter sent to practitioners of his nutritional system, not promotional literature to the masses.

Is he in the business of selling? Of course he is. So is T-Nation/Biotest. They have articles that promote their supplements. Do people get their panties in a bunch when T-Nation does this? Well bad example... there's people that get pissed about it here too. :slight_smile: God forbid anyone should make a profit on selling supplements.

If we could get back on topic here, and discuss the merits of this guys thesis. At least he has provided some references. I'd like to pick these apart with a fine tooth comb if anyones interested.

A disclaimer should be appropriate as well. This thread was not intended to by anti T-Nation/Biotest in any way as to degrade one of their supplements(Flameout). I'm interested in this topic purely as scientific curiosity. In the last few years Omega 3's have been touted as a miracle cure for almost everything. Has it gone overboard? Maybe, maybe not. If this guy's conclusions are bullshit I'd like to know.

And besides, isn't this website supposed to be "Bodybuilding's Think-tank". Where's all the scientific inquiry and debate?


#18

Bri,

It takes a lot of time and effort to go chase down references and break apart the details...

I'm not sure it's fair to expect many people to have that kind of time or energy available. You did get some very quick off the cuff comments, which don't take as much time and effort.


#19

This doesn't suprise me at all.
With the popularity among the nutrition community,it's about time they started taking heat.
I would'nt be suprised either if the drug companies started "research" showing omega 3's are unhealthy.

While omega 6 fatty acids are healthy,we consume too much of them;this could actually lead to some serious health problems.
Just stay away from anyone who advocates more omega 6's and less omega 3's(especially lobbyists).

The incidence of prostate cancer over the past 60 years has risen as dietary ratios of omega-3 and 6 fats have changed. Back at the end of World War II, omega-3 and omega-6 ratios were lopsided (1:2) in favor of omega-3s. Now, that ratio is 25:1 on the omega-6 side.


#20

Here are the abstracts to save people some work. :slightly_smiling:

1: J Neurochem. 1980 Oct;35(4):1004-7.

Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling.

Chan PH, Fishman RA.

The involvement of superoxide free radicals and lipid peroxidation in brain swelling induced by free fatty acids has been studied in brain slices and homogenates. The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3), arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in superoxide and membrane lipid peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect. Furthermore, superoxide formation was stimulated by NADPH and scavenged by the addition of exogenous superoxide dismutase in cortical slice homogenates. These in vitro data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the mechanism of polyunsaturated fatty acid-induced brain edema.

2: Brain Res. 1982 Sep 23;248(1):151-7.

Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells.

Chan PH, Fishman RA.

Effects of arachidonic acid on cellular metabolism, cation content, lipid peroxidation, sodium pump activities and release of labeled arachidonic acid were studied in C-6 glioma cells and N18TG2 neuroblastoma cells. Arachidonic acid caused a significant increase in intracellular sodium levels concomitant with a decrease in intracellular potassium in both cell lines. Both (Na+ + K+)-ATPase and p-nitrophenyl phosphatase of glioma cells were inhibited by arachidonic acid whereas only the p-nitrophenyl phosphatase of neuroblastoma cell was inactivated. Low concentrations of arachidonic acid stimulated lactic acid release whereas high concentrations had an opposite effect. In addition, the lipid peroxide content of glioma cells was increased abruptly by 50 microM arachidonic acid whereas only a slight increase of malondialdehyde was observed in neuroblastoma cells. When the cultured cells of both cell lines were incubated with exogenous labeled arachidonic acid, 78-95% of the label was incorporated into membrane phospholipids. Only a very small fraction of prostaglandin E2 and prostaglandin F2 alpha was synthesized. Exogenous arachidonic acid and free radicals generated with xanthine-xanthine oxidase caused a significant release of endogenous labeled arachidonic acid from cellular membrane phospholipids. These data further support our hypothesis that the arachidonic acid and its oxygen radical metabolites induce pathological alterations in membrane permeability and cellular volume.

3: J Neurochem. 1982 Feb;38(2):525-31.

Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices.

Chan PH, Yurko M, Fishman RA.

Cellular edema and increased lactate production were induced in rat brain cortical slices by xanthine oxidase and xanthine, in the presence of ferric dialdehyde, was increased 174%. Among the various subcellular fractions of brain cortex, xanthine oxidase-stimulated lipid peroxidation was highest in myelin, mitochondria, and synaptosomes, followed by microsomes and nuclei. Antioxidants, catalase, chlorpromazine, and butylated hydroxytoluene inhibited lipid peroxidation in both homogenates and synaptosomes, indicating H2O2 and radicals were involved. Further, several free fatty acids, especially oleic acid (18:1), arachidonic acid (20:4), and docosahexaenoic acid (22:6) were released from the phospholipid pool concomitant with the degradation of membrane phospholipids in xanthine oxidase-treated synaptosomes. These data suggest that lipases are activated by free radicals and lipid peroxides in the pathogenesis of cellular swelling.

4: J Neurosci Res. 1984;12(4):595-605.

Release of polyunsaturated fatty acids from phospholipids and alteration of brain membrane integrity by oxygen-derived free radicals.

Chan PH, Fishman RA, Schmidley JW, Chen SF.

We studied the effects of oxygen-derived free radicals on the ultrastructure of brain cortical slices and the release of fatty acids from phospholipids of crude synaptosomes. Xanthine oxidase, hypoxanthine, and ADP-Fe3+, a free-radical-generating system, caused swelling of cellular processes and mitochondria. The oxygen-derived free radicals also caused the rapid release and accumulation of endogenous polyunsaturated fatty acids (PUFA) from membrane phospholipids as determined by high-performance liquid chromatography (HPLC). Furthermore, [3H]-arachidonic acid was also rapidly released from prelabeled phospholipids concomitant with a decrease in radioactivity in various phospholipid fractions. The radioactivities of neutral lipids including diacylglycerols were unchanged by free radicals. These data indicate that the activation of phospholipase A2 and the release of PUFA may have overt effect on membrane integrity and the subsequent development of cellular injury and brain edema.

5: J Neurochem. 1988 Apr;50(4):1185-93.

Induction of intracellular superoxide radical formation by arachidonic acid and by polyunsaturated fatty acids in primary astrocytic cultures.

Chan PH, Chen SF, Yu AC.

Department of Neurology, University of California, School of Medicine, San Francisco 94143.

The effects of arachidonic acid and other polyunsaturated fatty acids (PUFAs) on both oxidative and metabolic perturbation were studied in primary cultures of rat cerebral cortical astrocytes. In the presence of 0.1 mM arachidonic acid, the rate of the reduction of nitroblue tetrazolium (NBT) to nitroblue formazan (NBF) was stimulated from 0.65 +/- 0.10 to 1.43 +/- 0.15 and from 0.092 +/- 0.006 to 0.162 +/- 0.009 nmol/min/mg protein in intact and broken cell preparations, respectively. The rate of superoxide radical formation, as measured by the superoxide dismutase (SOD)-inhibitable NBT reduction was 0.042 nmol/mg protein in broken cells and was negligible in intact cells. The latter is due to the impermeability of SOD into the intact cell preparation. NBF formation in intact astrocytes stimulated by arachidonic acid was both time- and dose-dependent. Other PUFAs, including linoleic acid, linolenic acid, and docosahexaenoic acid, were also effective in stimulating NBF formation in astrocytes, whereas saturated palmitic acid and monounsaturated oleic acid were ineffective. Similar effects of these PUFAs were observed in malondialdehyde formation in cells and lactic acid accumulation in incubation medium. These data indicate that both membrane integrity and cellular metabolism were perturbed by arachidonic acid and by other PUFAs. The sites of superoxide radical formation appeared to be intracellular and may be associated with membrane phospholipid domains, because liposome-entrapped SOD, which was taken up by intact astrocytes, reduced the level of superoxide radicals and lactic acid content, whereas free SOD was not effective.

6: J Neurosci Res. 1988 Aug;20(4):451-6.

Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia.

Hillered L, Chan PH.

Department of Neurology, School of Medicine, University of California, San Francisco 94143.

The aim of the present investigation was to evaluate the possible role of arachidonic acid and other free fatty acids in ischemia-induced mitochondrial dysfunction. Respiratory activities were measured in mitochondria isolated from rat brains subjected to 15-30 min of decapitation ischemia. Addition of bovine serum albumin (BSA) to the mitochondria, isolated in BSA-free media, abolished an ischemia-induced increase in substrate-stimulated (state 4) respiration but only partly reversed a marked inhibition of substrate-, phosphate-, and ADP-stimulated (state 3) respiration caused by the ischemia. Individual free fatty acids were measured in aliquots of the same mitochondrial preparations before and after treatment with BSA. There was a significant increase in arachidonic (20:4), stearic (18:0), palmitic (16:0), and docosahexaenoic (22:6) acid during ischemia. BSA treatment removed all 20:4 and reduced the amount of 18:0 and 16:0, but had no significant effect on 22:6. The main conclusions were 1) that 20:4, 18:0, and 16.0 were responsible for the partial uncoupling (increase in state 4 respiration) of mitochondrial respiration during ischemia, 2) that the inhibition of state 3 respiration caused by ischemia could only partly be attributed to an effect of FFAs, and 3) that the ischemia-induced mitochondrial dysfunction was caused by a combination of factors including 20:4.

7: J Neurosci Res. 1989 Oct;24(2):247-50.

Brain mitochondrial swelling induced by arachidonic acid and other long chain free fatty acids.

Hillered L, Chan PH.

Department of Neurology, University of California, School of Medicine, San Francisco 94143.

Polyunsaturated fatty acids (PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while monounsaturated and saturated long chain fatty acids do not possess this quality. This investigation has compared the ability of some free fatty acids (FFAs), known to be released during cerebral ischemia, to induce brain mitochondrial swelling in vitro. The PUFAs tested, especially arachidonic acid (20:4), were more potent in causing swelling than saturated or monounsaturated ones, as measured by the decrease in light absorbance of the mitochondrial suspension. This finding is in line with the unique potency of 20:4 to induce brain edema. Incubation of brain mitochondria with 20:4 for 20 min caused a dose-dependent swelling. ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of bovine serum albumin could only prevent but not reverse the swelling. The contraction of the swollen mitochondria appeared to be mediated by a mechanism dependent upon high-energy phosphates, potentiated by MgCl2. The concentration of 20:4 required to induce swelling was about 20 times higher than the concentration required to induce inhibition of mitochondrial respiratory function (L Hillered and P H Chan: J Neurosci Res 19:94-100, 1988a). Moreover, reversal of the swelling occurred without recovery of respiratory function. These results suggest that swelling is a phenomenon of minor importance as an indicator of brain mitochondrial dysfunction, at least when induced by 20:4 in vitro.

8: J Physiol. 1994 Feb 15;475(1):83-93.

Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.

Nishikawa M, Kimura S, Akaike N.

Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.

  1. The effect of docosahexaenoic acid (DHA) on N-methyl-D-aspartic acid (NMDA) responses in the presence of glycine was investigated in pyramidal neurons acutely dissociated from rat cerebral cortex in whole-cell and single channel configurations. 2. DHA potentiated the NMDA-induced response but reduced the non-NMDA (kainate-induced) response in a concentration-dependent manner at a holding potential of -60 mV under voltage-clamp conditions. 3. Arachidonic acid (AA) also potentiated the NMDA-induced response in a manner similar to DHA. Oleic acid caused a slight potentiation. However, other polyunsaturated and saturated fatty acids had no such effects. 4. The facilitatory action of DHA on the NMDA-induced response was not affected by adding inhibitors of cyclo-oxygenase, lipoxygenase or phospholipase A2, suggesting that DHA may exert its facilitatory effect directly on the NMDA receptor. 5. The facilitatory action of DHA was observed in the presence of a saturating dose of NMDA. Moreover, a detailed analysis of the NMDA receptor-operated single channel currents revealed that, in the presence of DHA, the open probability of the channel increased without changing the conductance, indicating that DHA may act by binding directly to a novel site on the NMDA receptor or by altering the lipid environment of the NMDA receptor and thereby potentiating the response to NMDA. 6. The results are discussed in terms of the possibility that DHA may play an important role in the genesis of long-term potentiation, at least that involving the activation of NMDA receptors.

Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line

9: Free Radic Biol Med. 2000 Oct 15;29(8):714-20.

Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures.

Lovell MA, Xie C, Markesbery WR.

Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.

Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F(2)-isoprostanes, and F(4)-neuroprostanes are present in the brain in patients with AD. Acrolein, an alpha,beta-unsaturated aldehydic product of lipid peroxidation has been demonstrated to be approximately 100 times more reactive than HNE and is present in neurofibrillary tangles in the brain in AD. We recently demonstrated statistically significant elevated concentrations of extractable acrolein in the hippocampus/parahippocampal gyrus and amygdala in AD compared with age-matched control subjects. Concentrations of acrolein were two to five times those of HNE in the same samples. Treatment of hippocampal cultures with acrolein led to a time- and concentration-dependent decrease in cell survival as well as a concentration-dependent increase in intracellular calcium. In cortical neuron cultures, we now report that acrolein causes a concentration-dependent impairment of glutamate uptake and glucose transport in cortical neuron cultures. Treatment of cortical astrocyte cultures with acrolein led to the same pattern of impairment of glutamate uptake as observed in cortical neuron cultures. Collectively, these data demonstrate neurotoxicity mechanisms of arolein that might be important in the pathogenesis of neuron degeneration in AD.

10: Lipids. 1996 Aug;31(8):829-37.

Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma lipid fractions and tissue phospholipids.

Cleland LG, Neumann MA, Gibson RA, Hamazaki T, Akimoto K, James MJ.

Rheumatology Unit, Royal Adelaide Hospital, Australia.

n-9 Eicosatrienoic acid (ETrA), also known as Mead acid, is a minor fatty acid in essential fatty acid (EFA)-sufficient healthy subjects but is found at increased levels in EFA deficiency. This study examined the influence of dietary ETrA from a biological source on plasma and tissue ETrA. A synthetic fat-free diet was prepared to which was added Mut 48 oil which contains 19% ETrA (wt%) as well as other n-9 fatty acids. Blends of vegetable oils were used to achieve overall diets with 5% fat (wt%) and varying amounts of ETrA at two different dietary levels of linoleic acid (LA), approximately 4.4 and 19% of total fatty acids. These diets were fed to 5-week-old Dark Agouti rats for four weeks. Plasma lipid fractions and liver, spleen, and peritoneal exudate (PE) cells were analyzed for fatty acid composition. ETrA was present at up to 20% total fatty acids in plasma triglyceride, cholesterol ester, and phospholipid fractions. ETrA also accumulated to substantial levels in phospholipids of liver and spleen (up to 15% of total fatty acids) and PE cells (up to 11%). ETrA was found in plasma and tissue phospholipids in proportion to the amount of ETrA present in the diet. The incorporation was reduced in diets with higher LA content compared to diets containing similar amounts of ETrA but lower LA. All rats remained apparently healthy, and histological survey of major organs revealed no abnormality. While the long-term implications for health of ingestion of diets rich in ETrA remain to be established, rats appear to tolerate high levels of dietary ETrA without adverse effects. Dietary enrichment with ETrA warrants further investigation for possible beneficial effects in models of inflammation and autoimmunity, as well as in other conditions in which mediators derived from n-6 fatty acids can affect homeostasis adversely.

11: Clin Exp Allergy. 2004 Feb;34(2):194-200.

Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants.

Stoney RM, Woods RK, Hosking CS, Hill DJ, Abramson MJ, Thien FC.

Department of Nutrition, The Alfred Hospital, Melbourne, Victoria, Australia.

BACKGROUND: Australia has one of the highest prevalence rates internationally of allergic conditions, such as asthma and eczema. Atopy is one hallmark for the development of allergic disease and predisposes to allergic inflammation in the target organs. omega-3 (n-3) fatty acids (FAs) are thought to act as precursors to the formation of less active inflammatory mediators, with the potential to reduce inflammation. OBJECTIVE: To investigate whether increased n-3 FA levels in maternal breast milk are associated with a lower risk of developing atopy in infancy. METHODS: Subjects were part of the prospective Melbourne atopy cohort study, which involved 620 children born into families where at least one first-degree relative had an atopic disease. Some 224 women (mean age 31.4+/-4.2 (SD) years, with 73.2% (n=164) having self-reported atopy) provided either a colostrum (n=194) or 3-month expressed breast milk (EBM) sample (n=118). Maternal colostrum and 3-month EBM samples were analysed for FA content by gas chromatography. Skin prick tests (SPTs) to six common allergens were performed on infants at 6, 12 and 24 months of age and on mothers who agreed at study entry. RESULTS: For infants sensitized to foods at 6 months (n=29), the total n-3 FA level in the colostrum was significantly higher (P=0.004) as were levels of individual long-chain n-3 FAs, docosoapentaenoic acid (DPA, C22:5, P=0.001) and docosahexaenoic acid (DHA, C22:6, P=0.002) than in non-sensitized infants. Infants with aero-allergen sensitization at 24 months (n=30) had higher levels of the n-3 FA, DPA (P=0.002) and DHA (P=0.007), and similarly higher total n-3 FA (P=0.009) in maternal colostrum than those infants who were not sensitized. CONCLUSION: Higher n-3 FA levels in the colostrum do not appear to confer protection against, but may be a risk factor for, the eventual development of atopy in high-risk breastfed infants.

12: Am J Psychiatry. 2004 Mar;161(3):567-9.

Comment in:
Am J Psychiatry. 2005 Feb;162(2):402; author reply 402-3.

Is low dietary intake of omega-3 fatty acids associated with depression?

Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lonnqvist J.

Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland. reeta.hakkarainen@ktl.fi

OBJECTIVE: This study examined the association between the dietary intake of omega-3 fatty acids and low mood, major depression, and suicide. METHOD: A total of 29,133 men ages 50 to 69 years participated in a population-based trial in Finland. The intake of fatty acids and fish consumption were calculated from a diet history questionnaire. Self-reported depressed mood was recorded three times annually, data on hospital treatments due to a major depressive disorder were derived from the National Hospital Discharge Register, and suicides were identified from death certificates. RESULTS: There were no associations between the dietary intake of omega-3 fatty acids or fish consumption and depressed mood, major depressive episodes, or suicide. CONCLUSIONS: Dietary intake of omega-3 fatty acids showed no association with low mood level.

And a few others...

13: Eur J Clin Nutr. 2003 Jun;57(6):793-800.

Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction.

Grundt H, Nilsen DW, Mansoor MA, Nordoy A.

Department of Clinical Chemistry, Central Hospital in Rogaland, POB 8100, 4068 Stavanger, Norway. heidi@madlalia.no

OBJECTIVE: To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins combined with n-3 PUFAs or corn oil. DESIGN: A prospective, randomised, double-blind, controlled study. SETTING: One hospital centre in Stavanger, Norway. SUBJECTS: A total of 300 subjects with an acute myocardial infarction (MI). INTERVENTIONS: Gelatine capsules, containing 850-882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation. RESULTS: After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA-MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA-MDA at 12 months follow-up, P=0.004.We found no impact of statins on TBA-MDA. CONCLUSION: TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment. SPONSORSHIP:: Pharmacia A/S and Pronova A/S, Norway.

14: Arterioscler Thromb Vasc Biol. 2000 Mar;20(3):708-14.

Oxidized cholesterol in the diet accelerates the development of atherosclerosis in LDL receptor- and apolipoprotein E-deficient mice.

Staprans I, Pan XM, Rapp JH, Grunfeld C, Feingold KR.

Department of Veterans Affairs Medical Center, University of California, San Francisco 94121, USA. stapan@itsa.ucsf.edu

The aim of the current study was to determine whether oxidized cholesterol in the diet accelerates atherosclerosis in low density lipoprotein receptor- (LDLR) and apolipoprotein E- (apo E) deficient mice. Mice were fed either a control diet or a diet containing oxidized cholesterol. For LDLR-deficient mice, the control diet consisted of regular mouse chow to which 1.0% cholesterol was added. The oxidized diet was identical to the control diet except that 5% of the added cholesterol was oxidized. In apo E-deficient mice, the control diet contained 0.15% cholesterol, whereas in the oxidized diet, 5% of the added cholesterol was oxidized. LDLR-deficient and apo E-deficient mice were fed the experimental diets for 7 and 4 months, respectively. In mice fed the oxidized-cholesterol diets, the levels of oxidized cholesterol in sera were increased. At the end of the experiment, aortas were removed and atherosclerosis was assessed. We found that in LDLR-deficient mice, feeding of an oxidized-cholesterol diet resulted in a 32% increase in fatty streak lesions (15.93+/-1.59% versus 21.00+/-1.38%, P<0.03). Similarly, in apo E-deficient mice, feeding of an oxidized-cholesterol diet increased fatty streak lesions by 38% (15.01+/-0.92% versus 20. 70+/-0.86%, P<0.001). The results of the current study thus demonstrate that oxidized cholesterol in the diet accelerates fatty streak lesion formation in both LDLR- and apo E-deficient mice.

15: Atherosclerosis. 2001 Mar;155(1):9-18.

Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil.

Song JH, Miyazawa T.

Department of Applied Biological Chemistry, Faculty of Agriculture, Tohoku University, 981-8555, Sendai, Japan.

The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different lipid types on lipid peroxidation was studied in rats. Each group of male Sprague-Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm oil (supplemented with 20% soybean oil) diet without DHA was fed as the control. Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The incorporation of dietary DHA into plasma and liver phospholipids was more pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased alpha-tocopherol levels in plasma and liver. In addition, liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.

16: Food Chem Toxicol. 1998 Aug;36(8):663-72.

The association of increasing dietary concentrations of fish oil with hepatotoxic effects and a higher degree of aorta atherosclerosis in the ad lib.-fed rabbit.

Ritskes-Hoitinga J, Verschuren PM, Meijer GW, Wiersma A, van de Kooij AJ, Timmer WG, Blonk CG, Weststrate JA.

Unilever Nutrition Centre, Unilever Research Laboratory, Vlaardingen, The Netherlands.

The long-term effects of consumption of marine long-chain n-3 polyunsaturated fatty acids (PUFA) on atherosclerosis in the rabbit were examined. Female Dutch rabbits were fed purified diets, containing 40 energy% total fat, for a period of 2.5 years. To study the dose response relationship between fish oil intake and atherosclerosis, four diets were formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fifth and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and linoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, blood samples were taken for determination of clinical chemical parameters, triacylglycerol and total cholesterol levels. Feeding 10 and 20 energy% fish oil containing diets, resulted in an increase of liver enzymes (AST, ALT and ALP). Histological evaluation of the liver also revealed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout the study. Total cholesterol levels in blood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A significant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. These results indicate that the long-chain n-3 polyunsaturated fatty acids in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding necessitates the exclusion of liver pathology in experimental studies on atherosclerosis in animal models.

17: Int J Circumpolar Health. 2001 Apr;60(2):143-9.

Cod liver oil consumption, smoking, and coronary heart disease mortality: three counties, Norway.

Egeland GM, Meyer HE, Selmer R, Tverdal A, Vollset SE.

National Health Screening Service, Research Department, P.O. Box 8155, 0033 Oslo, Norway. grace.egeland@isf.uib.no

It has been hypothesized that omega-3 fatty acid consumption may lessen the adverse effect of smoking on coronary heart disease (CHD) risk. Thus, we explored whether cod liver oil consumption was protective of coronary heart disease in a cohort of men and women participating in a cardiovascular disease screening in Norway. The study population was aged 35-54 at the time of the baseline screening conducted by the National Health Screening Service of Norway in 1977-1983. Of 56,718 age-eligible men and women, 52,138 participated, of whom 42,612 (82%) completed a dietary questionnaire. Cod liver oil use was reported by 12.5%. At baseline, cod liver oil users had lower triglycerides, adjusting for age, body mass index, time since last meal and income (p < or = .05). As of December 1992, 639 and 118 CHD deaths were observed among the men and women, respectively. Overall, we observed no effect of cod liver oil consumption reported at baseline and CHD mortality in Cox Proportional Hazards analyses [Hazard Ratio (HR) = 1.0 (0.8-1.3)]. In analyses, stratified by smoking status, never smokers and current smokers showed non-significant beneficial associations between cod liver oil use and CHD mortality (HR = 0.7, 95% CI = 0.4-1.5; and HR = 0.8, 95% CI = 0.6-1.2, respectively). However, among former smokers a non-significant excess risk of CHD mortality was associated with cod liver oil use (HR = 1.6, 95% CI = 0.9-2.6). Smokers, regardless of their cod liver oil use were at a substantially higher risk for CHD mortality relative to non-smokers. Omega-3 fatty acid supplementation, as practiced in this cohort, provided no significant benefits to CHD risk among study participants.

18: Lipids. 1997 Jul;32(7):745-51.

Unusual effects of some vegetable oils on the survival time of stroke-prone spontaneously hypertensive rats.

Huang MZ, Watanabe S, Kobayashi T, Nagatsu A, Sakakibara J, Okuyama H.

Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.

Preliminary experiments have shown that a diet containing 10% rapeseed oil (low-erucic acid) markedly shortens the survival time of stroke-prone spontaneously hypertensive (SHRSP) rats under 1% NaCl loading as compared with diets containing perilla oil or soybean oil. High-oleate safflower oil and high-oleate sunflower oil were found to have survival time-shortening activities comparable to that of rapeseed oil; olive oil had slightly less activity. A mixture was made of soybean oil, perilla oil, and triolein partially purified from high-oleate sunflower oil to adjust the fatty acid composition to that of rapeseed oil. The survival time of this triolein/mixed oil group was between those of the rapeseed oil and soybean oil groups. When 1% NaCl was replaced with tap water, the survival time was prolonged by approximately 80%. Under these conditions, the rapeseed oil and evening primrose oil shortened the survival time by approximately 40% as compared with n-3 fatty acid-rich perilla and fish oil; lard, soybean oil, and safflower oil with relatively high n-6/n-3 ratios shortened the survival time by roughly 10%. The observed unusual survival time-shortening activities of some vegetable oils (rapeseed, high-oleate safflower, high-oleate sunflower, olive, and evening primrose oil) may not be due to their unique fatty acid compositions, but these results suggest that these vegetable oils contain factor(s) which are detrimental to SHRSP rats.

19: Lipids. 1998 Jul;33(7):655-61.

Free fatty acid fractions from some vegetable oils exhibit reduced survival time-shortening activity in stroke-prone spontaneously hypertensive rats.

Miyazaki M, Huang MZ, Takemura N, Watanabe S, Okuyama H.

Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.

Previously, we demonstrated that several vegetable oils that included low-erucic rapeseed oil markedly shortened the survival time (by approximately 40%) of stroke-prone spontaneously hypertensive (SHRSP) rats as compared with perilla oil, soybean oil, and fish oil. We considered that a factor other than fatty acids is toxic to SHRSP rats, because the survival time-shortening activity could not be accounted for by the fatty acid compositions of these oils. In fact, a free fatty acid (FFA) fraction derived from lipase-treated rapeseed oil was found to be essentially devoid of such activity. A high-oleate safflower oil/safflower oil/perilla oil mixture exhibited a survival time-shortening activity comparable to that of rapeseed oil, but the activity of this mixed oil was also reduced by lipase treatment. A partially hydrogenated soybean oil shortened the survival time by approximately 40%, but a FFA fraction derived from lipase-treated partially hydrogenated soybean oil shortened it by 13% compared with soybean oil. Fatty acid compositions of the rapeseed oil and a FFA fraction derived from lipase-treated rapeseed oil were similar, but those of hepatic phospholipids of rats fed the oil and FFA were slightly but significantly different. These results support the interpretation that the survival time-shortening activity exhibited by some vegetable oils is due to minor components other than fatty acids, and that an active component(s) were produced in or contaminated soybean oil during the partial hydrogenation processes.

20: Br J Nutr. 2003 Oct;90(4):777-86.

Fish-oil supplementation reduces stimulation of plasma glucose fluxes during exercise in untrained males.

Delarue J, Labarthe F, Cohen R.

Laboratoire Regional de Nutrition Humaine & EA-948, Medecine 4-Nutrition, CHU Cavale Blanche, F-29200-Brest, France. jacques.delarue@univ-brest.fr

The present study examined the effects of a 3-week fish-oil supplementation (6 g/d) on the rate of plasma glucose disappearance (Rd glucose), hepatic glucose production (HGP), carbohydrate oxidation and lipid oxidation during exercise. Six untrained males (23+/-1 years; 67.6+/-2.7 kg) performed two 90 min cycling exercise sessions at 60 % of maximal O2 output separated by 20 d. During the 20 d before the first test, they ingested 6 g olive oil/d, then 6 g fish oil/d during the 20 d before the second test. Plasma glucose fluxes and lipolysis were traced using 6,6-[(2)H2]glucose and 1,1,2,3,3-[(2)H5]glycerol respectively. Substrates oxidation was obtained from indirect calorimetry. At rest HGP and the Rd glucose were similar after olive oil and fish oil (1.83 (SE 0.05) v. 1.67 (SE 0.11) mg/kg per min). During exercise, fish oil reduced the stimulation of both the Rd glucose (5.06 (SE 0.23) v. 6.37 (SE 0.12) mg/kg per min; P<0.05) and HGP (4.88 (SE 0.24) v. 5.91 (SE 0.21) mg/kg per min; P<0.05). Fish oil also reduced glucose metabolic clearance rate (6.93 (SE 0.29) v. 8.30 (SE 0.57) ml/min). Carbohydrate oxidation tended to be less stimulated by exercise after fish oil than after olive oil (12.09 (SE 0.60) v. 13.86 (se 1.11) mg/kg per min; NS). Lipid oxidation tended to be more stimulated by exercise after fish oil (7.34 (SE 0.45) v. 6.85 (SE 0.17) mg/kg per min; NS). Glycaemia, lactataemia, insulinaemia and glucagonaemia were similarly affected by exercise after fish oil and olive oil. Lipolysis at rest was similar after fish oil and olive oil (2.92 (SE 0.42) v. 2.94 (SE 0.28) micromol/kg per min) and similarly stimulated by exercise (6.42 (SE 0.75) v. 6.77 (SE 0.72) micromol/kg per min). It is concluded that fish oil reduced the Rd glucose by 26 % by reducing glucose metabolic clearance rate, possibly by facilitating fat oxidation, and reduced HGP by 21%, possibly by a feedback mechanism.

21: Endocrinology. 2003 Sep;144(9):3958-68.

Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production.

Holness MJ, Greenwood GK, Smith ND, Sugden MC.

Department of Diabetes and Metabolic Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 4NS, United Kingdom.

In healthy individuals, peripheral insulin resistance evoked by dietary saturated lipid can be accompanied by increased insulin secretion such that glucose tolerance is maintained. Substitution of long-chain omega-3 fatty acids for a small percentage of dietary saturated fat prevents insulin resistance in response to high-saturated fat feeding. We substituted a small amount (7%) of dietary lipid with long-chain omega-3 fatty acids during 4 wk of high-saturated fat feeding to investigate the relationship between amelioration of insulin resistance and glucose-stimulated insulin secretion (GSIS). We demonstrate that, despite dietary delivery of saturated fat throughout, this manipulation prevents high-saturated fat feeding-induced insulin resistance with respect to peripheral glucose disposal and reverses insulin hypersecretion in response to glucose in vivo. Effects of long-chain omega-3 fatty acid enrichment to lower GSIS were also observed in perifused islets suggesting a direct effect on islet function. However, long-chain omega-3 fatty acid enrichment led to hepatic insulin resistance with respect to suppression of glucose output and impaired glucose tolerance in vivo. Our data demonstrate that the insulin response to glucose is suppressed to a greater extent than whole-body insulin sensitivity is enhanced by enrichment of a high-saturated fat diet with long-chain omega-3 fatty acids. Additionally, reduced GSIS despite glucose intolerance suggests that either long-chain omega-3 fatty acids directly impair the beta-cell response to saturated fat such that insulin secretion cannot be augmented to normalize glucose tolerance or beta-cell compensatory hypersecretion represents a response to insulin resistance at the level of peripheral glucose disposal but not endogenous glucose production.