Dietary omega-3 LCPUFA intake in the prevention of neovascular age-related macular degeneration: a systematic review and meta-analysis / La ingesta de AGPICL omega-3 en la prevención de la degeneración macular neovascular relacionada con la edad: revisión sistemática y metaanálisis

Purpose: to evaluate the protective effect of omega-3 long-chain unsaturated fatty acids on the progression of wet age-related macular degeneration (wAMD). Methods: this meta-analysis was designed, implemented, and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol and is reported following PRISMA guidelines. Results: in this study we included 5 observational trials, including 2 cross-sectional studies, 2 case-control studies, and 1 confrontation study. These tests are conducted in the U.S., Europe and Japan, and are of high quality. In general, people with high dietary long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) have a lower risk of progression to advanced age-related macular degeneration (AMD) (effect size, ES: 0.51, 95 % CI [0.34, 0.75], I2 = 70 %, p = 0.01). When assessing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake and wAMD risk a total of the three above studies were included, which also produced similar results. Conclusions: the highest DHA consumption reduced the risk of disease by 39 % (effect size: 0.61, 95 % CI [0.50, 0.74], I2 = 14 %, p = 0.31); compared with the lowest EPA consumption, the highest EPA consumption reduced the risk of wAMD by 32 % (ES: 0.68, 95 % CI [0.57, 0.82], I2 = 39 %, p = 0.20) (AU)

Propósito: evaluar el efecto protector de los AGPICL omega-3 sobre la degeneración macular húmeda asociada a la edad (DMAE). Métodos: este metaanálisis fue diseñado, implementado y analizado de acuerdo con el protocolo de Metaanálisis de Estudios Observacionales en Epidemiología (MOOSE) y se informa siguiendo las directrices de PRISMA. Resultados: en este estudio se incluyeron 5 ensayos observacionales, entre ellos 2 estudios transversales, 2 estudios de casos y controles y 1 estudio de confrontación. Estos ensayos se realizan en Estados Unidos, Europa y Japón y son de alta calidad. En general, las personas con una dieta alta en ácidos grasos poliinsaturados de cadena larga (AGPICL omega-3) tienen un menor riesgo de progresión hacia la degeneración macular avanzada relacionada con la edad (DMAE) (tamaño del efecto, ES: 0,51, IC 95 % [0,34, 0,75], I2 = 70 %, p = 0,01). Al evaluar la ingesta de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) y el riesgo de DMAE se incluyeron en total tres de los estudios anteriores, que también arrojaron resultados similares. Conclusiones: el mayor consumo de DHA redujo el riesgo de enfermedad en un 39 % (tamaño del efecto: 0,61, IC del 95 % [0,50, 0,74], I2 = 14 %, p = 0,31); en comparación con el menor consumo de EPA, el mayor consumo de EPA redujo el riesgo de wAMD en un 32 % (ES: 0,68, IC del 95 % [0,57, 0,82], I2 = 39 %, p = 0,20) (AU)

Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men.

BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil are postulated to have favourable effects on platelet, endothelial and vascular function. We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA. METHODS AND RESULTS: Following a 2 wk run-in taking encapsulated refined olive oil, 48 healthy young men were randomly allocated using a parallel design to receive EPA-rich (3.1 g EPA/d) or DHA-rich (2.9 g DHA/d) triglyceride concentrates or refined olive oil (placebo), for a total supplementary lipid intake of 5 g/d. The specified primary outcome was change in platelet monocyte aggregates (PMA); secondary outcomes were capillary density, augmentation index, digital pulse volume measurements, 24 h ambulatory BP, plasma 8-isoprostanes-F2α. Changes in the proportions of DHA and EPA in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention. There was no significant treatment effect on PMA (P = 0.382); mean changes (%) (95% CI) were placebo -0.5 (-2.0, 1.04), EPA 0.4 (-0.8, 1.6), DHA 0.3 (-1.5, 2.0). R-QUICKI, an index of insulin sensitivity, was greater following EPA compared to placebo (P < 0.05). No other significant differences were noted. CONCLUSION: Neither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males. This trial was registered at clinicaltrials.gov as NCT01735357.

Arachidic acid in extender improves post-thaw parameters of cryopreserved Nili-Ravi buffalo bull semen.

Cryopreservation process reduces lipids and phospholipids from buffalo bull spermatozoa. It was therefore hypothesized that supplementation of fatty acid to extender may improve the post-thaw quality of buffalo semen. The objective was to evaluate the effect of arachidic acid supplementation in extender on post-thaw quality of buffalo bull (Bubalus bubalis) spermatozoa. Semen was collected from three adult Nili-Ravi buffalo bulls of similar age group with artificial vagina (42°C) for 3 weeks (replicate). Qualified semen ejaculates (n = 18) were split into four aliquots and diluted in tris-citric acid extender containing 0.0 (control), 5.0, 10.0 and 20.0 ng/ml at 37°C having approximately 50 × 10(6) spermatozoa/ml. Diluted semen was cooled to 4°C in 2 h and equilibrated for 4 h at 4°C. Cooled semen was filled in 0.5-ml straws at 4°C, kept on liquid nitrogen vapours for 10 min and plunged in liquid nitrogen for storage. Thawing of frozen semen was performed after 24 h at 37°C for 30 s. Sperm progressive motility (%) was improved in a dose-dependent manner by supplementing arachidic acid at 5.0, 10.0 and 20.0 ng/ml compared with control. Structural and functional integrity of sperm plasma membrane (%), number of acrosome-intact live sperm (%) and sperm chromatin integrity (%) were better (p < 0.05) in extender having 5.0 ng/ml of arachidic acid compared with control. At 10.0 ng/ml, these values did not vary (p > 0.05) from those at 5.0 ng/ml. Further improvement in structural and functional integrity of sperm plasma membrane, number of acrosome-intact live sperm and chromatin integrity was observed at 20.0 ng/ml of arachidic acid in extender. In conclusion, arachidic acid supplementation in extender improved the post-thaw quality parameters of cryopreserved Nili-Ravi buffalo bull spermatozoa. Among the arachidic acid concentrations studied, maximum improvement in post-thaw semen quality parameters was observed at 20.0 ng/ml.

18-MEA and hair appearance.

The effects of the removal of 18-MEA on the dynamic contact angle (advancing contact angle and receding contact angle) and friction force (friction force microscopy (FFM)) were examined in the present study. Chemically untreated hair tresses formed more finely ordered bundles, with the fibers aligned more parallel to each other, in the wet state, and lying flat and aligned parallel to each other in the dry state. Hair tresses in which 18-MEA had been removed by potassium t-butoxide treatment formed coarser tangled bundles and were aligned in a disorderly manner in the wet state, causing the hair to become entangled and disorderly in the dry state. This was because the 18-MEA-removed hair fibers adhered to each other and were not easy to realign in the wet state. The distorted part of the bundle dried faster and the tress shape was eventually fixed in the entangled shape. One role of 18-MEA is to allow hair fibers to lie flat and parallel with respect to each other in the wet state by providing relatively high receding contact angles and low surface friction. Hair alignment in the dry state is directly affected by hair alignment in the wet environment, particularly in the case of damaged hair.

Deposition of 18-MEA onto alkaline-color-treated weathered hair to form a persistent hydrophobicity.

A technology for the deposition of a persistent hydrophobicity to alkaline-color-treated weathered hair surfaces using 18-MEA (18-methyleicosanoic acid) is presented. Two approaches were examined in order to make 18-MEA bind tightly to the alkaline-color-treated weathered hair surface. One was to apply 18-MEA as an acid form and the other was to apply 18-MEA as a salt or complex. It was found that the combination of 18-MEA with specific cationic surfactants [stearoxypropyldimethylamine (SPDA) and docosyldimethylamine (DSDA)] makes the alkaline-color-treated weathered hair surface hydrophobic and that its hydrophobicity is maintained even after shampooing. Characterization of adsorbed layers of 18-MEA/SPDA on a mica surface, as a possible hydrophilic surface model, was performed using atomic force microscopy (AFM) and angle-resolved X-ray photoelectron spectroscopy (AR-XPS). The results revealed that 18-MEA/SPDA formed a layer with high wear resistance, with an alkyl chain, the hydrophobic moiety, oriented at an angle of around 25 degrees to the air interface.

Hypocholesterolemic effects of fatty acid bile acid conjugates (FABACs) in mice.

Fatty acid bile acid conjugates (FABACs) prevent and dissolve cholesterol gallstones and prevent diet induced fatty liver, in mice. The present studies aimed to test their hypocholesterolemic effects in mice. Gallstone susceptible (C57L/J) mice, on high fat (HFD) or regular diet (RD), were treated with the conjugate of cholic acid with arachidic acid (FABAC; Aramchol). FABAC reduced the elevated plasma cholesterol levels induced by the HFD. In C57L/J mice, FABAC reduced plasma cholesterol by 50% (p<0.001). In mice fed HFD, hepatic cholesterol synthesis was reduced, whereas CYP7A1 activity and expression were increased by FABAC. The ratio of fecal bile acids/neutral sterols was increased, as was the total fecal sterol excretion. In conclusion, FABACs markedly reduce elevated plasma cholesterol in mice by reducing the hepatic synthesis of cholesterol, in conjunction with an increase of its catabolism and excretion from the body.

Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease.

The balance of intake of n-6 and n-3 PUFA, and consequently their relative incorporation into immune cells, is important in determining the development and severity of immune and inflammatory responses. Some disorders characterised by exaggerated inflammation and excessive formation of inflammatory markers have become among the most important causes of death and disability in man in modern societies. The recognition that long-chain n-3 PUFA have the potential to inhibit (excessive) inflammatory responses has led to a large number of clinical investigations with these fatty acids in inflammatory conditions as well as in healthy subjects. The present review explores the presence of dose-related effects of long-chain n-3 PUFA supplementation on immune markers and differences between healthy subjects and those with inflammatory conditions, because of the important implications for the transfer of information gained from studies with healthy subjects to patient populations, e.g. for establishing dose levels for specific applications. The effects of long-chain n-3 PUFA supplementation on ex vivo lymphocyte proliferation and cytokine production by lymphocytes and monocytes in healthy subjects have been studied in twenty-seven, twenty-five and forty-six treatment cohorts respectively, at intake levels ranging from 0.2 g EPA+DHA/d to 7.0 g EPA+DHA/d. Most studies, particularly those with the highest quality study design, have found no effects on these immune markers. Significant effects on lymphocyte proliferation are decreased responses in seven of eight cohorts, particularly in older subjects. The direction of the significant changes in cytokine production by lymphocytes is inconsistent and only found at supplementation levels > or =2.0 g EPA+DHA/d. Significant changes in inflammatory cytokine production by monocytes are decreases in their production in all instances. Overall, these studies fail to reveal strong dose-response effects of EPA+DHA on the outcomes measured and suggest that healthy subjects are relatively insensitive to immunomodulation with long-chain n-3 PUFA, even at intake levels that substantially raise their concentrations in phospholipids of immune cells. In patients with inflammatory conditions cytokine concentrations or production are influenced by EPA+DHA supplementation in a relatively large number of studies. Some of these studies suggest that local effects at the site of inflammation might be more pronounced than systemic effects and disease-related markers are more sensitive to the immunomodulatory effects, indicating that the presence of inflamed tissue or 'sensitised' immune cells in inflammatory disorders might increase sensitivity to the immunomodulatory effects of long-chain n-3 PUFA. In a substantial number of these studies clinical benefits related to the inflammatory state of the condition have been observed in the absence of significant effects on immune markers of inflammation. This finding suggests that condition-specific clinical end points might be more sensitive markers of modulation by EPA+DHA than cytokines. In general, the direction of immunomodulation in healthy subjects (if any) and in inflammatory conditions is the same, which indicates that studies in healthy subjects are a useful tool to describe the general principles of immunomodulation by n-3 PUFA. However, the extent of the effect might be very different in inflammatory conditions, indicating that studies in healthy subjects are not particularly suitable for establishing dose levels for specific applications in inflammatory conditions. The reviewed studies provide no indications that the immunomodulatory effects of long-chain n-3 PUFA impair immune function or infectious disease resistance. In contrast, in some conditions the immunomodulatory effects of EPA+DHA might improve immune function.

The impact of EPA and DHA on blood lipids and lipoprotein metabolism: influence of apoE genotype.

Fish and fish oil-rich sources of long-chain n-3 fatty acids have been shown to be cardio-protective, through a multitude of different pathways including effects on arrhythmias, endothelial function, inflammation and thrombosis, as well as modulation of both the fasting and postprandial blood lipid profile. To date the majority of studies have examined the impact of EPA and DHA fed simultaneously as fish or fish oil supplements. However, a number of recent studies have compared the relative biopotency of EPA v. DHA in relation to their effect on blood lipid levels. Although many beneficial effects of fish oils have been demonstrated, concern exists about the potential deleterious impact of EPA and DHA on LDL-cholesterol, with a highly-heterogenous response of this lipid fraction reported in the literature. Recent evidence suggests that apoE genotype may be in part responsible. In the present review the impact of EPA and DHA on cardiovascular risk and the blood lipoprotein profile will be considered, with a focus on the apoE gene locus as a possible determinant of lipid responsiveness to fish oil intervention.

Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans.

BACKGROUND: Supplementation of the diet with fish oil, which is rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is reported to decrease several markers of immune function. However, whether EPA, DHA, or a combination of the 2 exerts these immunomodulatory effects is unclear. OBJECTIVE: The objective of the study was to determine the effects of supplementation with an EPA-rich or DHA-rich oil on a range of immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes in healthy humans. DESIGN: In a placebo-controlled, double-blind, parallel study, 42 healthy subjects were randomly allocated to receive supplementation with either placebo (olive oil), EPA (4.7 g/d), or DHA (4.9 g/d) for 4 wk. Blood samples were taken before and after supplementation. RESULTS: The fatty acid composition of plasma phospholipids and neutrophils was dramatically altered by supplementation with EPA or DHA, and the effects of EPA differed notably from those of DHA. DHA supplementation decreased T lymphocyte activation, as assessed by expression of CD69, whereas EPA supplementation had no significant effect. Neither the EPA-rich oil nor the DHA-rich oil had any significant effect on monocyte or neutrophil phagocytosis or on cytokine production or adhesion molecule expression by peripheral blood mononuclear cells. CONCLUSIONS: Supplementation with DHA, but not with EPA, suppresses T lymphocyte activation, as assessed by expression of CD69. EPA alone does not, therefore, influence CD69 expression. No other marker of immune function assessed in this study was significantly affected by either EPA or DHA.

Changes of HDL subfractions by eicosapentaenoic acid intake and physical load in 20- to 25-year-old men.

The effects of daily eicosapentaenoic acid (EPA) intake and physical activity on high-density lipoprotein (HDL) subfraction, which may be an index of health status, were examined. The HDL subfraction, triglyceride and T-chol levels in the serum of 10 male volunteers aged 20-25 were examined before, immediately after and 1 h after being subjected to a physical load by bicycle ergometer at 90 W for 20 min. Subjects were then given 1.25 g EPA/day for 2 weeks, and the above test was repeated. By EPA intake, the distribution of HDL3b and 3c decreased significantly by 16.8 and 15.3%, respectively, and that of 2b increased significantly by 17.9%. The rate of change of subfraction of the 29th part (2b) of 30 parts in the total range of HDL increased by 67%, and decreased by 47% in 7th part (3c). By physical load, the distribution of HDL2a increased significantly by 15.4%, while 3b tended to decrease. By physical load after EPA intake, the distribution of 2a decreased significantly by 9.7%, and those of 3b and 3c increased significantly by 20.5 and 5.4%, respectively, and that of the 7th part (3c) increased by 37%. Thus, the physical load after EPA intake is effective to prevent arteriosclerosis as increasing the rate of change of HDL3c and as showing the longevity pattern of the HDL subfraction. Concentration of TG in a modal HDL pattern group increased by 95% after EPA intake, but that of a bimodal group did not show any change. HDL-cholesterol level in the bimodal group was higher than that in the modal group, especially after EPA intake. Two type III subjects changed to type IV by the load and the EPA intake, respectively. Thus, it seemed that the transformation from a modal pattern to a bimodal pattern by a certain lifestyle, especially regular physical activity and proper food intake, is a very important trial for the prevention of cerebrovascular diseases.

Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer.

Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer. This study aimed to evaluate the acceptability and effects of oral supplementation with high-purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six patients were entered into the study. EPA (95% pure) was administered as free acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and then a maintenance dose of 6 g/day was administered. Patients were assessed before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body composition, hematologic and clinical chemistry variables, acute-phase protein response, and performance status. Overall survival was noted. Supplementation was well tolerated, with only five patients experiencing side effects possibly attributable to the EPA. Before starting EPA, all patients had been losing weight at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was stable. After four weeks of EPA supplementation, patients had a median weight gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this stabilization of weight persisted over the 12-week study period. Total body water as a percentage of body weight remained stable, as did the proportion of patients with an acute-phase protein response, patients' nutritional intake, and performance status. Overall median survival from diagnosis in this study was 203 days. This study suggests that EPA is well tolerated, may stabilize weight in cachectic pancreatic cancer patients, and should be tested as an anticachectic agent in controlled trials.

beta-Carotene storage in rat organs following carrier mediated supplementation.

One rat group was supplemented with beta-carotene (BC) both in beadlets and the crystalline form in arachidic oil as a carrier added to standard diet; another rat group was given 1 ml crystalline BC-arachidic oil by gavage twice a week. In both rat groups, each rat ingested 350 mg BC/week for 12 weeks. The animals were then sacrificed and BC levels together with retinyl palmitate presence were assessed by HPLC analysis in liver, lung, kidney, small intestine, mesenteric fat, brain, spleen, stomach and blood plasma. In the first group, high BC storage, ranging from 4.2 to 45.2 nmols/g wet tissue, was found in liver, small intestine, spleen; lesser BC levels were found in lung, kidney, stomach, blood serum; retinyl palmitate was found in liver and lung. In the second group BC levels ranging from 0.5 up to 5,763 nmols/g wet tissue were detected in all organs, except for brain and stomach; the highest levels were in the lung; retinyl palmitate was detected in liver. The lung appeared to be a target organ for BC, as confirmed by its presence in the lungs of control rats fed standard diet and given 1 ml of arachidic oil alone by gavage twice a week.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.

Two patients with infantile phytanic acid storage disease (infantile Refsum disease), one of whom showed the presence of morphologically normal peroxisomes in a liver biopsy, were treated with a low phytanic acid diet for more than 2 years and the effects of treatment on certain clinical, biochemical and ultrastructural parameters were examined. Both patients showed evidence of either an improvement or stabilisation in their clinical condition. Plasma phytanic acid levels decreased to near normal values in approximately 6 weeks after the introduction of the diet; plasma pipecolic acid also declined markedly but the decrease was not so rapid and its level remained abnormal. C26:C22 fatty acid ratios decreased very slowly and even after 2 years the values remained grossly abnormal. Despite the marked reduction of phytanic acid in the liver, there was an increase in the C26:C22 fatty acid ratios and this appeared to be paralleled by an increase in inclusion bodies. Our data suggest that some patients with the infantile form of Refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid.

Site of the action of a synthetic atrial natriuretic peptide evaluated in humans.

The renal site of the natriuretic effect of human, atrial natriuretic peptide (hANP) was studied using clearance techniques in eight salt-loaded normal volunteers undergoing maximal water diuresis. Lithium was used as a marker of proximal sodium reabsorption. According to a two-way, single blind, crossover design, hANP (Met12-(3-28)-eicosahexapeptide, (2 micrograms/min) or its vehicle (Ve) were infused for two hours, followed by a two-hour recovery period. Blood pressure, heart rate and insulin clearance remained unchanged. During hANP infusion, the filtration fraction increased slightly from 19.6 to 24.3% (P less than 0.001), fractional water excretion rose transiently at the beginning of the infusion. Fractional excretion of sodium increased markedly from 2.2% to 7.4% (P less than 0.001) but remained unchanged with Ve. ANP increased fractional excretion of lithium slightly from 46 to 58% (P less than 0.01), while it remained stable at 47% during Ve. The distal tubular rejection fraction of sodium calculated from sodium and lithium clearances rose markedly from 4.7 to 13% (P less than 0.001) and returned to 6.2% at the end of the recovery period. Thus, under salt loading and water diuresis conditions, hANP infusion did not alter GFR, but reduced proximal reabsorption of sodium, and markedly enhanced the fraction of sodium escaping distal tubular reabsorption, suggesting that hANP-induced natriuresis is due, for an important part, to inhibition of sodium reabsorption in the distal nephron.

Production of eicosanoids by deendothelialized rabbit aorta: interaction between platelets and vascular wall in the synthesis of prostacyclin.

Production of eicosanoids by deendothelialized aorta in response to continuous infusions of arachidonic acid and platelet suspensions was determined in a rabbit aorta perfusion model. 6-keto-PGF1 alpha production was stimulated by AA infusion in a dose-related manner. Infusion of AA at 4 micrograms/ml/min led to an initial production rate of 0.64 +/- 0.29 ng/min which gradually increased to 0.93 +/- 0.11 ng/min at the 20th min of infusion. When the concentration of AA infusion was increased to 10 micrograms/ml/min, 6-keto-PGF1 alpha production increased to 1.14 +/- 0.86 ng/min initially but declined with time. PGE2 production in response to AA 10 micrograms/min/ml was steady at around 5 ng/min while PGF2 alpha and TXB2 production were only slightly above the control. Perfusion of rabbit washed platelet suspensions at a rate of 3 X 10(8) plt/ml/min raised 6KPGF1 alpha production. The production was further increased when platelets were pretreated with 1-benzylimidazole (5 mM), along with a concurrent reduction in TXB2 release. Pretreatment of platelets with aspirin, on the other hand, abolished the increase in 6KPGF1 alpha production. Our data indicated that the vascular smooth muscle cells can efficiently utilize PGH2 produced by platelets to synthesize PGI2.

Refsum's disease: management by diet and plasmapheresis.

A case of Refsum's disease treated by serial plasma exchanges together with a moderate low phytanate diet is reported. Serial plasma exchanges determined a rapid significant clinical improvement (neuropathy and cerebellar ataxia) that allowed immediate return to full-time employment. The initial improvement could be maintained by intermittent serial plasmapheresis despite partial failure of the initially introduced low phytanate diet bringing 20 mg phytanic acid daily. A new dietary regimen bringing 10 mg phytanic acid was later introduced that was well tolerated. No liquid formula was used. The clinical improvement was clearly correlated to a fall in serum phytanic acid from 45.3 to 16.2 mg/100 ml.

Phytanic acid storage disease: hearing maintained after 15 years of dietary treatment.

Heredopathia atactica polyneuritiformis is a biochemically defined disease with a specific dietary treatment. It is an autosomal inborn error of metabolism. The phytanic acid is of exogenous origin and stems mainly from preformed phytanic acid in foods. In two Norwegian patients, serum phytanic acid has been brought down to normal levels and one of them has been followed for 15 years. During this period of dietary treatment there was no worsening of hearing.

[Refsum's disease: 10 years of a diet low in phytanic acid and phytol]. / Maladie de Refsum: Dix ans de régime diététique pauvre en acide phytanique et phytol.

The authors report the evolution of two cases of Refsum's disease, treated with a specific phytol and phytanic acid diet for ten years. This treatment is effective leading to a rapid and stable fall of phytanemia, and a progressive improvement of the peripheral neuropathy and cerebellous symptoms, then prevent from quite new aggravation. Any symptom in favour of a cardiac, pulmonary or renal disease was observed during the past ten years. On the other hand, the sight and hearing disorders remained unchanged and are responsible to a major discomfort in this long-dated evolution. The strict liquid diet is quickly abandoned on account of a bad tolerance (diarrhea), but the ordinary diet is better endured, and is sufficient to keep a low phytanemia; this need a permanent continuation.