Essential fatty acids (EFAs) are believed to be vital to the growing fetus because they are involved in the development of cell membranes, including those in the brain. The body also uses them as precursors for the synthesis of ecosanoids (e.g. prostaglandin compounds), and possibly have a role in energy production.
– the omega-6 family: derived particularly from plant oils (such as linoleic acid and arachidonic acid)
– the omega-3 family: derived particularly from fish oils (such as gamma-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
The body converts EFAs by lengthening them. The EFAs towards the end of the metabolic process are called long chain polyunsaturated fatty acids (LCPFAs).
Study one: EFAs and problem solving in infants
Research just published in The Lancet has confirmed the crucial role that LCPFAs appear to play in the development of the brain during the earliest weeks of infancy.
Subjects: Forty-four full-term formula-fed infants from a Scottish hospital.
Method: The infants were randomized to receive either a formula enriched with LCPFAs or one without enrichment. They took the assigned formula from birth to 4 months of age, and were then tested for problem solving ability six months later (i.e. when aged 10 months).
Problem solving ability was scored using a method which assesses the child’s ability to reach a toy when they have to show some degree of planning. For example, getting the toy after they have seen it hidden under a cover. The i” >Tts were scored on any behavior which expressed the
intention to solve the problem, as well as on successfully getting the toy.
Results: The LCPFA-supplemented formula infants did significantly better in problem solving at 10 months of age than the control infants Table: Median scores for problem solving at 10 months of age.
Ref: Lancet 1998;352:688-91
Study two: EFAs and growth in pre-term infants
Arachidonic acid status is related to intra-uterine rather than post-natal growth. On the other hand, dietary DHA is important to brain growth in the first 6 weeks after birth. These are the conclusions from the authors of a recent Dutch study.
Subjects: 143 low birth weight infants (<= 2500gm, gestational age 30-41 weeks)
Method: Arachidonic acid and DHA were measured during days 10 to 42 after birth. Infants received pre-term formula either with or without LCPFAs, while another group was given maternal milk. Anthropometric measures and growth rates were assessed.
Results: Red cell arachidonic acid levels at 10 days of age significantly correlated (p<0.05) with various measures of intra-uterine growth in formula-fed infants, including birth weight and a composite score for weight, length and head circumference. It also correlated with birth weight
in breast fed infants.
DHA red cell levels correlated with brain weight on days 10 and 42 in formula-fed infants (accounting for 21-34% of the variance in brain growth parameters)
Ref: Eur J Pediatr, 1998; 157:146-52
Study three: EFAs and visual acuity
A new study from Denmark found no significant correlation between visual acuity and the amount of EFA in formula given to full-term infants.
Subjects: Thirty-seven full-term Danish infants.
Method: They were randomiz rest average age of 25 days to receive two weeks
of one of three formulas:
i. Enriched with DHA and gamma-linolenic acid
ii Enriched with DHA only
iii. Standard formula without LCPFAs
There were 17 breast-fed controls.
Visual acuity evoked potential was measured at 4 months of age.
Results: There was a significant relationship overall between visual acuity and feeding (breast fed infants had better visual acuity than the combined EFA supplemented group, which in turn was better than the control infants:
However, there was no significant correlation between visual acuity and individual formulas.
Ref: J Pediatr Gastroenterol Nutr, 1998;26:412-21
Clinical studies on the importance of EFAs in fetal and infant development are a relatively new and exciting area of nutrition. These three papers help convey some of that excitement.
The growing fetus is unusually dependent on maternal LCPFAs in particular, because it has limited ability to synthesize them from their shorter chain precursors (such as linoleic and linolenic acid). This applies to the fetus and in early infancy.
Premature babies are especially dependent on the EFA content of breast milk or formula, because their premature birth has deprived them of precious time in the uterus when they should have been building up their own LCPFA stores.
Breast milk is normally a good source of LCPFAs. But a combination of inadequate EFA in the mother’s diet, prematurity and use of infant formula with not enough of the right kind of EFA could potentially lead to a LCPFA deficiency, with clinical consequences. The question is: what kind of consequences?
The relationship between LCPFA levels and neural tube development was first identified in relation to visual acuity in the early 1990’s. However, the exact nature of the connection is still being explored.
The Danish study above does not find a significant correlation in full-term infants, but other studies have (e.g. see Pediatr Res 1993;34:425-427). However, the Danish researchers only started supplementing the infants after three weeks.
The overall weight of evidence suggests that LCPFA supply both in pregnancy and infancy DOES have an influence on visual acuity and neural development, and that this is especially important in premature infants.
The results from Scotland summarized in study one above are therefore particularly important, as they are in full-term infants and measure cognitive development near the end of the first year of life. Previous studies have tended to concentrate on visual acuity testing during the
first month or two. The Dutch results confirm the particular importance of LCPFAs in the early growth of low birth weight infants.
Overall there is plenty of reason to get excited about this field of research. Studies such as these are showing us that EFAs have significant impacts on brain development and growth. Manufacturers of infant formula are paying particular attention. It was not that long ago that they began to offer EFA-enriched formula, but mainly using shorter chain EFAs such as linoleic and linolenic. We are now beginning to see infant formulas with more concentrated LCPFA content.
One crucial link in the chain of better care for infants is that it is very easy to influence the levels of LCPFAs in the growing fetus and infant. Dietary enrichment for the mother readily increases EFA levels in pregnancy
and in breast milk. The formula-fed baby infant’s levels can also be easily increased by supplementing the formula.
This is quite unlike iron (or even calcium), where supplementing the mother does not seem to influence the breast milk much (although it helps the mother).
In summary, this research may open up asule to provide simple, cost-effective interventions that can help infants in a practical way, particularly in regions where fish (especially deep sea fish – the richest source of LCPFAs) are abundant.
Nutrition 1998 Jul-Aug;14(7-8):627-33
Immunonutrition: the role of omega-3 fatty acids.
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
The dietary fatty acids of the omega-3 series are rapidly incorporated into cell membranes and profoundly influence biological responses. These lipids influence membrane stability, membrane fluidity, cell mobility, the formation of receptors, binding of ligands to their receptors, activation of intracellular signaling pathways either directly or through the formation of eicosanoids, gene expression, and cell differentiation. In general, eicosanoids formed from the omega-3 fatty acids are much less potent in causing biological responses than those formed from the omega-6 fatty acids, including stimulation of cytokine production and inflammatory responses. In well-controlled clinical studies, consumption of omega-3 fatty acids has resulted in reduction of cardiovascular diseases including arrhythmias and hypertension, protection from renal disease, improvement in rheumatoid arthritis, improvement in inflammatory bowel diseases, reduced episodes of rejection, and protection from infection. The interactions between the omega-3 fatty acids and pharmacologic drugs that alter intracellular signaling pathways are only now being studied.
Rev Med Chil 1991 Mar;119(3):267-72
Active rheumatoid arthritis: effect of dietary supplementation with omega-3 oils. A controlled double-blind trial.
Astorga G, Cubillos A, Masson L, Silva JJ
Departamento de Medicina (Seccion Reumatologia), Facultad de Medicina, Universidad de Chile, Santiago.
We evaluated the effect of dietary supplementation with eicosapentaenoic acid in 8 patients with active rheumatoid arthritis. An appropriate placebo was given in a randomized double blind fashion to 8 control subjects. After 12 weeks of therapy a significant improvement in prehensile function was detected in patients receiving active treatment, other clinical parameters remaining unchanged. No significant side effects were detected. A larger trial may help define a possible therapeutic role for omega-3 fatty acids in patients with rheumatoid arthritis.
Proc Nutr Soc 1998 Nov;57(4):555-62
Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease.
School of Chemical and Life Sciences, University of Greenwich, London, and UK. Harbige@greenwich.ac.uk
Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatt/A>. In contrast, in both T-cell and antibody-mediated autoimmune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be appreciated that linoleic acid does not reflect the functions of dihomo-gamma-linolenic and arachidonic acid, and that the endogenous rate of conversion of linoleic to arachidonic acid is slow (Hassam et al. 1975, 1977; Phylactos et al. 1994; Harbige et al. 1995). In addition to effects of dietary fatty acids on immunoregulation, inflammation as a consequence of immune activation in autoimmune disease may also be an important mechanism of action whereby dietary fatty acids modulate disease activity. In conclusion, regulation of gene expression, signal transduction pathways, production of eicosanoids and cytokines, and the action of antioxidant enzymes are all mechanisms by which dietary n-6 and n-3 fatty acids may exert effects on the immune system and autoimmune disease. Probably the most significant of these mechanisms in relation to our current understanding of immunoregulation and inflammation would appear to be via fatty acid effects on cytokines. The amount, type and balance of dietary fatty acids and associated antioxidant nutrients appear to impact on the immune system to produce immune-deviation or immunosuppressive effects, and to reduce immune-mediated inflammation which will in turn affect the susceptibility to, or severity of, autoimmune disease.
An Med Interna 1990 Jun;7(6):299-303
The hypolipemic effect of concentrated salmon oil rich in n-3 fatty acids.
Perez Corral F, Perales J, Fraile G
Servicio de Medicina Interna, Hospital Ramon y Cajal, Madrid.
The lipid-lowering effect of a concentrated salmon oil, rich in n-3 fatty acids was tested as a supplement to the normal diet of 27 patients with high levels of cholesterol and/or triglycerides, during 2 months. The results of the study confirmed that addition of n-3 fatty acid to diets produced a reduction of plasma levels of lipids. The most significant reduction of plasma levels is of the blood lipids. The most significant reduction was observed in triglycerides in patients with high levels (from 295.8 to 219.8 mg/dl) (p = 0.001), as well as the whole group (from 231 to 180 mg/dl) (p = 0.002). At the same time, there was a reduction of cholesterol in all patients (from 295 to 268.4 mg/dl) (p = 0.001), including those whose cholesterol was higher (from 316.2 to 284.9 mg/dl) (p = 0.002). We concluded that the use of compounds rich in n-3 fatty acids showed an important plasma lipid-lowering effect, playing a significant role in hyperlipidemic patient control.
Diabetes Care 1991 Dec;14(12):1160-79
Biological effects of omega-3 fatty acids in diabetes mellitus.
Malasanos TH, Stacpoole PW
University of Texas Health Science Center, Department of Pediatrics, San Antonio 78284.
Fish oils exert important biological effects on several pathways predisposing to atherosclerosis. Epidemiological studies provided the initial evidence that omega-3 fatty acids may be the principal factor in fish oils responsible for these effects and have led to several short-term clinical trials in which fish-oil concentrates have been administered to various populations at risk for coronary heart disease, including patients with diabetes mellitus. Omega-3 fatty acids reduce serum lipids and lipoproteins, impair platelet aggregation, increase cell membrane fluidity, and lower blood pressure in humans. In this review, we highlight these and other potentially antiatherogenic properties of marine lipids in diabetic subjects.
Am J Clin Nutr 1995 Oct;62(4):761-8
Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder.
Stevens LJ, Zentall SS, Deck JL, Abate ML, Watkins BA, Lipp SR, Burgess JR
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907-1264, USA.
Attention-deficit hyperactivity disorder (ADHD) is the term used to describe children who are inattentive, impulsive, and hyperactive. The cause is unknown and is thought to be multifactorial. Based on the work of others, we hypothesized that some children with ADHD have altered fatty acid metabolism. The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects. Also, a subgroup of 21 subjects with ADHD exhibiting many symptoms of essential fatty acid (EFA) deficiency had significantly lower plasma concentrations of 20:4n-6 and 22:6n-3 than did 32 subjects with ADHD with few EFA-deficiency symptom0006he data are discussed with respect to cause, but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.
Ugeskr Laeger 1996 Jul 15;158(29):4195-8
Painful menstruation and low intake of n-3 fatty acids.
Specialkursus i Husholdning, Aarhus Universitet.
Menstrual pain, dysmenorrhea, which is known to be prostaglandin mediated, can possibly be influenced by the dietary ratio of omega-3 and omega-6 polyunsaturated fatty acids. The prostaglandins derived from marine omega-3 fatty acids are normally less aggressive and therefore expected to be associated with milder menstrual symptoms. This hypothesis was surveyed in an epidemiological study in Danish women based upon self administered questionnaires concerning menstrual history, present symptoms, general health, socio-economic factors, and general dietary habits. Two prospective four-day dietary records were used to estimate average daily nutrient intake. The subjects were recruited by advertising they were 20-45 years of age, not pregnant, and did not use oral contraceptives. No correlations were found between socioeconomic or anthropometric data and menstrual problems. However, certain dietary habits e.g. low intakes of animal and fish products, and low intakes of specific nutrients (omega-3 PUFA, B12 and omega-3/omega-6 ratio) were correlated with menstrual pain. The other nutrients in the diet were not significantly related to menstrual pain. The results were highly significant and mutually consistent and supported the hypothesis that a higher intake of marine, omega-3 fatty acids correlate with milder menstrual symptoms.
Am J Obstet Gynecol 1996 Apr;174(4):1335-8
Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents.
Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL
Division of Adolescent Medicine, Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
OBJECTIVES: The purpose of the study was to examine whether dietary supplementation with omega-3 fatty acids can relieve symptoms of dysmenorrhea in adolescents. STUDY DESIGN: Forty-two adolescents with dysmenorrhea were randomly allocated to two groups. In the first group 21 girls received fish oil (1080 mg icosapentaenoic acid, 720 mg docosahexaenoic acid, and 1.5 mg vitamin E) daily for 2 months followed by a placebo for an additional 2 months. In the second group 21 girls received placebo for the first 2 months, followed by fish oil for 2 more months. The Cox Menstrual Symptom Scale was used to assess response to treatment. RESULTS: There were no significant differences in the Cox Menstrual Symptom Scale between the two groups at baseline after 2 months of placebo administration. After 2 months of treatment with fish oil there was a marked reduction in the Cox Menstrual Symptom Scale from a baseline mean value of 69.9 to 44.0 (p < 0.0004). CONCLUSIONS: This study suggests that dietary supplementation with omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents.
Ann N Y Acad Sci 1993 Jun 14;683:35-45
Dietary fats, fish, and blood pressure.
University Department of Medicine, Royal Perth Hospital, Australia.
In humans any effects of dietary saturated fats or omega-6 polyunsaturates on blood pressure appear to be mediated by changes in caloric intake and long-term weight changes. In contrast, omega-3 fatty acids have a mild antihypertensive effect, which is seen most clearly in untreated subjects with higher blood pressures, in older people, and during sodium restriction. The mechanism may be due to a combination of effects consequent to incorporation of omega-3 fatty acids into vascular phospholipids, leading to reduced formation of endothelial contractile substances in larger vessels and impairment of sympathetic neuroeffector and other vasoconstrictor mechanisms in resistance vessels.
Am J Gastroenterol 1992 Apr;87(4):432-7
Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study.
Aslan A, Triadafilopoulos G
Gastroenterology Section, Veterans Affairs Medical Center, Martinez, California.
Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease. Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa, and these levels tend to correlate with severity of the disease. In this study, we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month, double-blind, placebo-controlled, crossover trial of dietary supplementation with fish oil, which provided about 4.2 g of omega-3- fatty acids per day. A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mucosal leukotriene B4 production was measured by radioimmunoassay. Mean disease activity index declined 56% for patients receiving fish oil and 4% for patients on placebo (p less than 0.05). There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels. All patients tolerated fish oil ingestion and showed no alteration in routine blood studies. No patient worsened; anti-inflammatory drugs could be reduced or eliminated in eight patients (72%) while receiving fish oil. We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production, compared with placebo therapy. Further studies are needed to elucidate the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis.
Ann Intern Med 1992 Apr 15;116(8):609-14
Dietary supplementation with fish oil in ulcerative colitis.
Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W
Jewish Hospital of St. Louis, Missouri 63110.
OBJECTIVE: To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, crossover trail with 4-month treatment periods (fish oil and placebo) separated by a 1-month washout. SETTING: Four gastroenterology divisions. PATIENTS: Twenty-four patients with active ulcerative colitis entered the study. Five dropped out, and one was noncompliant. Eighteen patients completed the study. All patients had active disease as manifested by diarrhea and rectal inflammation. INTERVENTIONS: Treatment with prednisone and sulfasalazine was continued. Fish oil supplementation consisted of 18 Max-EPA (eicosapentaenoic acid) capsules daily (eicosapentaenoic acid, 3.24 g; and docosahexaenoic acid, 2.16 g). Placebo supplementation consisted of 18 identical capsules containing isocaloric amounts of vegetable oil. MEASUREMENTS: Patients were evaluated at study entry and after each diet period. Evaluations included a review of symptoms, flexible sigmoidoscopy, rectal biopsy, and rectal dialysis to measure prostaglandin E2 and leukotriene B4 levels. RESULTS: Fish oil supplementation resulted in a significant decrease in rectal dialysate levels of leukotriene B4 from 71.0 to 27.7 pg/mL (average change, -43.3 pg/mL; 95% CI, -83 to -3.6). Significant improvements were seen in acute histology index (average change, -8.5 units from a baseline of 10.5 units; CI, -12.9 to -4.2) and total histology index (average change, -8.5 units from a baseline of 14.80; CI, -13.2 to -3.8) as well as significant weight gain (average weight gain, 1.74 kg, CI, 0.94 to 2.54). No significant changes occurred in any variable during the placebo period. Seven patients received concurrent treatment with prednisone. During the fish oil supplementation period, the mean prednisone dose decreased from 12.9 mg/d to 6.1 mg/d and rose from 10.4 mg/d to 12.9 mg/d during the placebo diet period (P greater than 0.20). CONCLUSIONS: Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain.
Fertil Steril 1998 Jul;70(1):81-8
Relation of endometriosis and neuromuscular disease of the gastrointestinal tract: new insights.
Mathias JR, Franklin R, Quast DC, Fraga N, Loftin CA, Yates L, Harrison V
Woman’s Hospital of Texas, Houston 77054, USA.
OBJECTIVE: To investigate the neuromuscular activity of the gastrointestinal tract by antroduodenal manometry in women with endometriosis documented by laparoscopy, to assess the effects of diet and drug therapy on symptoms, and to assess the bacterial overgrowth that is commonly associated with these nerve diseases. DESIGN: Prospective, open-label study. SETTING: A clinical center for the care of women’s health. PATIENT(S): Fifty women with endometriosis documented by laparoscopy and gastrointestinal tract symptoms characterized by chronic abdominal pain, nausea, vomiting, early satiety, bloating and distention, and altered bowel habits. INTERVENTION(S): Motility of the gastrointestinal tract was recorded and bacterial overgrowth was assessed. Treatment consisted of dietary changes, including reduction of glycemic carbohydrates, balancing with omega 9 oils, elimination of foods with caffeine and tyramine, and addition of omega 3 fatty acids, as well as drug therapy with clonazepam (0.25 mg 3 times per day). RESULT(S): All 50 women showed a characteristic motility change (ampulla of Vater-duodenal wall spasm, a seizure equivalent of the enteric nervous system). Forty of the women showed bacterial overgrowth. There was a significant reduction in the total symptom score after 8 weeks of treatment. CONCLUSION(S): This study suggests that endometriosis and gastrointestinal tract symptoms are a result of the dysfunction of hollow organs. Correction of the biochemical imbalance of the eicosanoid system and the hypersecretion of insulin that results from excessive intake of glycemic carbohydrates and lack of essential fatty acids significantly decreases symptoms in patients with endometriosis and associated neuromuscular disease of the gastrointestinal tract.
Clin Tech Small Anim Pract 1998 Nov; 13(4):211-6
Interventional nutrition for gastrointestinal disease.
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
Nutritional intervention plays a key role in the successful management of gastrointestinal disease. This article focuses on several novel areas of nutritional intervention that are becoming increasingly important in gastrointestinal disease, including short-chain fatty acids, omega-3 polyunsaturated fatty acids and glutamine. Short-chain fatty acids are the principal end-products of bacterial fermentation of dietary fibers and have profound effects on normal intestinal cell metabolism and proliferation. Short-chain fatty acids have the potential to improve overall intestinal health, stimulate intestinal healing, and decrease intestinal inflammation. Omega-3 fatty acids, from dietary sources or supplements, may also be useful in decreasing intestinal inflammation and in preventing intestinal cancer. Finally, glutamine also may play an important role in the nutritional management of gastrointestinal disease