Yoshiyuki Ishikura

Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction

Age-dependent increase of peroxidation of membrane fatty acids such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) in neurons was reported to cause a decline of the hippocampal long-term potentiation (LTP) and cognitive dysfunction in rodents. Although supplementation of ARA and DHA can improve LTP and cognitive function in rodents, their effects in humans are unknown. The present work was undertaken to study whether ARA and DHA have beneficial effects in human amnesic patients. The subjects were 21 mild cognitive dysfunction (12 MCI-A with supplementation and 9 MIC-P with placebo), 10 organic brain lesions (organic), and 8 Alzheimers disease (AD). The cognitive functions were evaluated using Japanese version of repeatable battery for assessment of neuropsychological status (RBANS) at two time points: before and 90 days after the supplementation of 240 mg/day ARA and DHA, or 240 mg/day of olive oil, respectively. MCI-A group showed a significant improvement of the immediate memory and attention score. In addition, organic group showed a significant improvement of immediate and delayed memories. However, there were no significant improvements of each score in AD and MCI-P groups. It is suggested from these data that ARA and DHA supplementation can improve the cognitive dysfunction due to organic brain damages or aging.

Effects of arachidonate-enriched triacylglycerol supplementation on serum fatty acids and platelet aggregation in healthy male subjects with a fish diet

The changes in fatty acid composition of serum and in platelet aggregation induced by supplementation of arachidonate-enriched TAG were investigated in twenty-four healthy Japanese men in a double-blind, placebo-controlled study. The arachidonate-enriched TAG ingested was an edible oil, extracted and purified from a biomass of submerged fermented Mortierella alpina. Mean daily intake of fish and shellfish by subjects was 87.2 (se5.3) g/d, while dietary intakes of arachidonic acid (ARA) by the ARA group and placebo group were 175 (se12) and 179 (se13) mg/d, respectively. In the ARA group, after 2-week supplementation of 838 mg ARA/d, ARA concentration in serum phospholipids was increased from 9.6 (se0.4) to 13.7 (se0.4) g/100 g total fatty acids, and was significantly different from that in the placebo group (P < 0.001). This level was maintained for 4 weeks but returned to baseline level after a 4-week washout period. Linoleic acid concentration in serum phospholipids decreased from 19.2 (se0.8) to 16.3 (se0.6) g/100 g total fatty acids in the ARA group. Similarly, ARA content of serum TAG increased after ARA supplementation. Neither the EPA nor DHA content of serum phospholipids or TAG was altered by ARA supplementation. The platelet aggregation induced in platelet-rich plasma by adding adenosine diphosphate, collagen and ARA, physical characteristics of subjects, and biochemical parameters were unchanged throughout the test period. These findings suggest that ARA concentration in serum phospholipids and TAG can be safely increased by supplementation of arachidonate-enriched TAG oil.

Supplementation of arachidonic acid-enriched oil increases arachidonic acid contents in plasma phospholipids, but does not increase their metabolites and clinical parameters in Japanese healthy elderly individuals: a randomized controlled study

BackgroundThe importance of arachidonic acid (ARA) among the elderly has recently gained increased attention. The effects of ARA supplementation in the elderly are not fully understood, although ARA is considered to be associated with various diseases. We investigate whether ARA supplementation to Japanese elderly subjects affects clinical parameters involved in cardiovascular, inflammatory, and allergic diseases. We also examine the levels of ARA metabolites such as prostanoids during intervention.MethodsWe conducted a randomized, double-blind and placebo-controlled parallel group intervention trial. ARA-enriched oil (240 or 720 mg ARA per day) or placebo was administered to Japanese healthy men and women aged 55-70 years for 4 weeks followed by a 4-week washout period. The fatty acid contents of plasma phospholipids, clinical parameters, and ARA metabolites were determined at baseline, 2, 4, and 8 weeks.ResultsThe ARA content in plasma phospholipids in the ARA-administrated groups increased dose-dependently and was almost the same at 2 weeks and at 4 weeks. The elevated ARA content decreased to nearly baseline during a 4-week washout period. During the supplementation and washout periods, no changes were observed in eicosapentaenoic acid and docosahexaenoic acid contents. There were no changes in clinical blood parameters related to cardiovascular, inflammatory and allergic diseases. ARA supplementation did not alter the level of ARA metabolites such as urinary 11-dehydro thromboxane B2, 2,3-dinor-6-keto prostaglandin (PG) F1α and 9,15-dioxo-11α-hydroxy-13,14-dihydro-2,3,4,5-tetranor-prostan-1,20-dioic acid (tetranor-PGEM), and plasma PGE2 and lipoxin A4. ARA in plasma phospholipids was not correlated with ARA metabolite levels in the blood or urine.ConclusionThese results indicate that ARA supplementation, even at a relatively high dose, does not increase ARA metabolites, and suggest that it does not induce cardiovascular, inflammatory or allergic diseases in Japanese elderly individuals.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. Objective: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). Methods: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. Results: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months’ supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). Conclusion: Three months’ supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Arachidonic Acid Supplementation Decreases P300 Latency and Increases P300 Amplitude of Event-Related Potentials in Healthy Elderly Men

In the present study, we examined the effects of arachidonic acid (ARA) on age-related event-related potential (ERP) changes in 25 healthy elderly men. This study was performed using a double-blind crossover design. The subjects were administered 600 mg/day of ARA-enriched triglyceride (SUNTGA40S; containing 240 mg ARA) in capsules or the same amount of olive oil in capsules as an inactive placebo for 1 month. ERPs were measured before capsule administration and after 1 month of administration, and P300 latency and amplitude were also measured. In subjects administered 240 mg/day ARA, P300 latency was significantly shorter, and P300 amplitude was significantly higher than in those administered olive oil capsules, and they exhibited a significant increase in ARA content in serum phospholipids. These findings suggest that supplementation of ARA can improve cognitive function in healthy elderly men.