オメガ３脂肪酸、ＤＨＡの医学、獣医学的根拠

人や犬と猫の関節疾患、腎臓病、膵炎、がん、腫瘍の予防や治療などに幅広く効果を示す事が知られているオメガ３脂肪酸は特にＤＨＡが最も効果的であり多くの論文や学会発表がなされています。

ここで１０の論文や発表文などの内容を簡単に紹介し、最後に Abstract 等の原文を載せておきますので興味ある方はご覧下さい。

 

その１　オメガ３脂肪酸 犬猫の慢性腎臓病の改善と延命

 

飽和脂肪またはオメガ – 6脂肪酸を豊富に含む食事を摂取した犬と比較し、オメガ – 3 脂肪酸を補充した食事を摂取した犬は死亡率が低く、腎機能に優れ、腎病変および蛋白尿の発生も低く、コレステロール値も低かった。 オメガ – 3 脂肪酸食を摂取した犬では、実際に腎機能が改善された。
自然発生の慢性腎臓病罹患猫でオメガ – 3脂肪酸濃度が最も高い食事を摂取した猫が最も長く生存した。
Proceedings, The 15th Congress of FAVA　慢性腎臓病の栄養管理
カリフォルニア大学 Veterinary Medical Center – San Diego 腎臓/泌尿器/血液透析科コーディネータ

 

その２　オメガ３脂肪酸、リンパ腫の犬に対する延命効果

 

32匹のリンパ腫の犬の試験で、抗がん剤の治療とともに食事にオメガ３脂肪酸とアルギニン加えると、無病期間と生存期間が有意に延長したことを伝えています。
コロラド州立大学医学部獣医学部の比較腫瘍学グループの発表
Cancer. 2000 Apr 15;88(8):1916-28.

 

その３　オメガ３脂肪酸は人の慢性腎臓病の進行を抑える

 

最近の研究でオメガ３脂肪酸の補給によってIgA腎症患者の腎機能喪失率を低下させることが示された。
透析患者においてはオメガ3脂肪酸の補給を行うことで、有益な影響がある事を伝えた。
総血漿オメガ３脂肪酸レベルが低い高齢者は、3年間の追跡調査でクレアチニンクリアランスが大きく低下する。
これらの発見から、オメガ３脂肪酸をより多く摂取する事が慢性腎臓病の進行を遅らせるであろうことが推察される。
Curr Pharm Des. 2009; 15(36): 4149–4156.

 

その４　ＤＨＡ、ＤＰＡを豊富に含む藻類オイルは抗炎症作用が強い

 

in vivoと In vitroの試験で、DPAn-6は抗炎症活性を持ち、加えてDHAの効果を高めることが判明。
DPAを含むDHAリッチオイルはインドメタシンに近い抗炎症作用を示した事を伝えています。
Lipids. 2010 May;45(5):375-84. doi: 10.1007/s11745-010-3406-3. Epub 2010 Apr 4.

 

その５　オメガ３脂肪酸は人の膵臓がんの予防に寄与

 

日本の国立がんセンターのグループが２０１５年にAmerican Journal of Clinical Nutritionで論文発表した内容です。
がん既往歴のない82,024人を対象とし、１２〜１５年間膵臓がんの罹患状況を調査。
オメガ３脂肪酸、DHA摂取には膵臓がん罹患リスクの低下と関連がみられ、膵臓がんの予防に寄与することを伝えています。

 

その６　オメガ３脂肪酸は急性膵炎、慢性膵炎に良い

 

脂質が慢性膵炎に与える影響（日本医事新報社、Web医事新報）の中でオメガ３脂肪酸は急性膵炎とともに，慢性膵炎の進展を抑制できる可能性がある事を伝えています。

 

その７　オメガ３脂肪酸は乳がんのリスクを下げる

 

オメガ３脂肪酸が乳がんを予防するかを調べたフランスの研究。
浸潤性の非転移性乳癌を有する241人の患者および良性乳房疾患を有する88人の患者の脂肪組織の脂肪酸組成を調べ
オメガ３脂肪酸特にＤＨＡは乳がんの予防の役割を果たす可能性がある事を伝えています。
International Journal of Cancer 98(1):78-83 · April 2002 with 92 Reads

 

その８　オメガ３脂肪酸はラットの乳腺腫瘍の成長を妨げる

 

ラット乳腺腫瘍の成長はオメガ３脂肪酸で抑制され、抗酸化作用のあるビタミンＥを加えた場合には逆に腫瘍の成長が促進された。
さらに酸化促進剤を添加すると腫瘍の成長が抑制されたことも伝えています。

（抗酸化作用のあるビタミンEは癌や腫瘍には良くない）
Nutrition and Cancer 36(1):33-41 · February 2000

 

その９　オメガ３脂肪酸は犬のリンパ腫、血管肉腫に良い効果

 

コロラド州立大学獣医学部のグループが、血管肉腫の13匹の犬とリンパ腫の66匹の犬でオメガ３脂肪酸を加えた食事の摂取によって血小板機能の悪い変化は確認されず、臨床的に重大な出血を誘発しなかったことを報告しています。
J Vet Intern Med. 1999 Nov-Dec;13(6):574-80.

 

その１０　ＤＨＡは乳腺腫瘍の放射線治療の効果を高める。

 

高ＤＨＡ含有オイル（ＤＨＡ４０％を含むオイル）を食事に加えた場合腫瘍サイズは、照射後12日で60％減少したのに対し、対照群では31％、DHAとビタミンE群では36％減少した。
ＤＨＡは放射線治療の効果を高める事が判明。
抗酸化作用のあるビタミンEはＤＨＡの効果を妨げる事も判明。
（抗酸化物質であるビタミンEはがん治療の妨げとなる事がこの研究でも証明された。）
Int J Cancer. 2004 Apr 10;109(3):449-54.

 

 

オメガ３脂肪酸についてはこちらのページも参考にして下さい。⇒　犬・猫とオメガ３脂肪酸

 

 

PubMed等の原文

 

その１

Diagnosis and Management of Chronic Kidney Disease in Dogs and Cats

Omega-3 polyunsaturated fatty acids

The optimum quantity of omega-3 PUFA supplementation and ratio of omega-3/omega-6 PUFA appropriate for renal diets have not been conclusively established. Although prospective clinical trials evaluating the efficacy of additional omeg-3 polyunsatuarted fatty acid supplementation in dogs and cats with naturally occurring disease have not yet been performed, dietary supplementation with omega-3 PUFA’s have been shown to be beneficial in dogs with induced CKD. Compared with dogs fed diets high in saturated fats or omega-6 PUFA, dogs consuming a diet

supplemented with omega-3 PUFA had lower mortality, better renal function, fewer renal lesions, less proteinuria, and lower cholesterol levels. In dogs fed the omega-3 PUFA diet, renal function actually increased and remained above baseline over 20 months of study. Lesions of glomerulosclerosis, tubulointerstitial fibrosis, and interstitial inflammatory cell infiltrates were also reduced in dogs fed the diet supplemented with omega-3 PUFA’s. These benefits are thought to accrue, at least in part, by modification in prostanoid, thromboxane, and leukotriene production with anti- inflammatory, anti-thrombotic and antioxidant effects. Published data supporting the use of omega 3 polyunsaturated fatty acids in cats is limited to a single retrospective study of cats with spontaneous CKD in which cats surviving the longest were receiving the diet with the highest omega-3 PUFA concentration.

 

その２

Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study.

Abstract

BACKGROUND:

Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy.

METHODS:

Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores.

RESULTS:

Dogs fed the experimental diet had significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with controls. Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels were significantly (P < 0.05) associated with longer DFI and ST for dogs with Stage III lymphoma fed the experimental diet.

CONCLUSIONS:

Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma.

 

その３

Omega-3 and Renal Function in Older Adults

Abstract

Chronic kidney disease (CKD) is a major public health problem and can result in end-stage renal disease with need for dialysis or transplantation. In Europe up to 12% of the adult population had some renal impairment, while in the United States the end stage of CKD has increased dramatically from 209.000 in 1991 to 472.000 in 2004. Diabetes and hypertension are major causes of kidney pathology. Infection, particularly ascending infection, is more common with increasing age, as both immune function declines and associated pathology predisposing to infection, such as obstructive uropathy, becomes more common. Most pathological changes in the kidney appear to be initiated by oxidative stress, followed by an inflammatory reaction. Oxidative stress results from an imbalance between free radicals and their detoxification by endogenous and exogenous scavengers, including polyunsatured fatty acids (PUFA). Recent studies showed that PUFA supplementation slowed the rate of loss of renal function in patients with IgA nephropathy. Then, studies of omega-3 supplementation in dialysis patients describe salutary effects on triglyceride levels and dialysis access patency. We examined the relationship between total plasma PUFA levels and change in creatinine clearance over a three-year follow-up in the older persons enrolled in the InCHIANTI study, a population-based epidemiology study conducted in Tuscany, Italy. This study showed that older adults with low total plasma PUFA levels have a greater decline in creatinine clearance over three years of follow-up. These findings suggest that a higher dietary intake of PUFA may be protective against progression to chronic kidney disease.

 

その４

Docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn-6) algal oils reduce inflammatory mediators in human peripheral mononuclear cells in vitro and paw edema in vivo.

Abstract

The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA. In addition, DPAn-6 decreased intracellular levels of cyclooxygenase-2 (COX-2) and was a potent inhibitor of pro-inflammatory prostaglandin E2 (PGE2) production. DHA/DPAn-6-rich DHA-S (DHA-S) algal oil was more effective at reducing edema in rats than DHA-rich DHA-T (DHA-T), suggesting that DPAn-6 has anti-inflammatory properties. Further in vivo analyses demonstrated that feeding DPAn-6 alone, provided as an ethyl ester, reduced paw edema to an extent approaching that of indomethacin and enhanced the anti-inflammatory activity of DHA when given in combination. Together, these results demonstrate that DPAn-6 has anti-inflammatory activity and enhances the effect of DHA in vitro and in vivo. Thus, DHA-S algal oil may have potential for use in anti-inflammatory applications.

 

その５

Fish, n-3 PUFA consumption, and pancreatic cancer risk in Japanese: a large, population-based, prospective cohort study.

Abstract

BACKGROUND:

Most previous prospective studies in Western countries found no association between consumption of fish and n-3 (ω-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), for which the main source is fish, and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption.

OBJECTIVE:

We investigated the association between fish and n-3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women.

DESIGN:

The Japan Public Health Center-based Prospective Study (JPHC study) has enrolled 140,420 subjects. We analyzed data on 82,024 eligible participants aged 45-74 y without a history of cancer who responded to a validated food-frequency questionnaire that included 138 items in 1995 for cohort I and in 1998 for cohort II. Participants were followed through 2010. HRs and corresponding 95% CIs for the highest compared with lowest quartile were calculated by using multivariable-adjusted Cox proportional hazards regression models.

RESULTS:

During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. After the exclusion of pancreatic cancer cases in the first 3 y of follow-up, we found an inverse association of marine n-3 PUFA (EPA+DPA+DHA) and DHA consumption with pancreatic cancer risk: compared with the lowest quartile, multivariate-adjusted HRs in the highest quartile were 0.70 (95% CI: 0.51, 0.95; P-trend = 0.07) and 0.69 (0.51, 0.94; P-trend = 0.03), respectively. Associations for total fish, n-3 PUFA, EPA, and DPA consumption were similar but were not significant.

CONCLUSION:

High n-3 PUFA, especially marine n-3 PUFAs, and DHA consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption, although the data apply to only a portion of the JPHC study subjects.

 

その６

脂質が慢性膵炎に与える影響（日本医事新報社、Web医事新報）

脂肪が慢性膵炎を発症，進展させるメカニズムについては明らかでないが，慢性膵炎患者の食事調査や動物実験から，高脂肪食とアルコールの組み合わせが慢性膵炎を悪化させる因子であることが明らかになっている。

脂肪はCCK（コレシストキニン）の分泌を促進する因子である。高脂肪食の摂取によって，CCK分泌は強く刺激を受け，膵液の分泌量が増加する。また，動物性脂肪とアルコールの組み合わせは，膵液の粘稠度を増加させる（文献1）。したがって，高脂肪食（特に動物性脂肪）とアルコールをともに摂取することで，膵管内圧や膵組織内圧が著明に上昇し，膵酵素の異所性（膵組織内）の活性化が生じる。その結果，膵腺房細胞周囲の炎症細胞浸潤や，膵星細胞（線維化に関与する細胞）の活性化が生じる。そのため，高脂肪食とアルコール摂取の繰り返しは，膵腺房細胞の脱落や，膵実質の不規則な線維化などの慢性変化をもたらす原因になる。

オリーブオイルが膵組織に与える影響を検討した報告はないが，動物性脂肪と植物性脂肪の影響について報告がある。

アルコールに加え動物性脂肪と植物性脂肪を別々に投与し，膵の線維化を比較したところ（文献2），動物性脂肪投与群で膵の線維化が強くみられたと報告されている。また，先に述べた通り，アルコールと動物性脂肪の組み合わせは膵液の粘稠度を増加させ，膵管内圧上昇をもたらす。

しかし一方で，慢性的なアルコール投与のラットに植物性脂肪に多く含まれている多価不飽和脂肪酸を大量投与すると，膵腺房細胞障害が生じるという報告（文献3）がある。また，オリーブオイルの主成分であるオレイン酸は慢性膵炎モデルラットを作成する際に用いられ（文献4），膵障害をきたす脂肪酸として知られている。したがって，オリーブオイルは動物性脂肪よりは膵腺房細胞障害が少ない可能性はあるが，過剰摂取は避けなければならない。ちなみに，ω3系脂肪酸は急性膵炎とともに，慢性膵炎の進展を抑制できる可能性があるとの報告がある（文献5）。

高脂肪食は慢性膵炎の発症，進展因子であり，脂肪摂取は代償期の腹痛や急性増悪の危険因子である。このため，脂肪制限食が慢性膵炎の食事療法と考えられがちである。しかし，脂肪制限食はあくまで腹痛時や急性増悪時のみに施行する。代償期の腹痛がない時期（間歇期）や非代償期には，40～60g／日程度の脂肪摂取が必要（文献6）である。漫然とした脂肪制限の継続は，必須脂肪酸の欠乏や脂溶性ビタミン，微量元素の欠乏を招く危険性があるため，好ましくない。

 

その７

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France

Abstract

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer.

 

その８

Effect of an alpha-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status.

Cognault S1, Jourdan ML, Germain E, Pitavy R, Morel E, Durand G, Bougnoux P, Lhuillery C.

Author information

1

Laboratoire de Nutrition et Sécurité Alimentaire, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.

Abstract

To investigate whether the oxidative status of an 18:3(n-3) polyunsaturated fatty acid (PUFA)-enriched diet could modulate the growth of chemically induced rat mammary tumors, three independent experiments were performed. Experiments I and II examined the variation of tumor growth by addition of antioxidant (vitamin E) or a prooxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to a 15% linseed oil diet rich in 18:3(n-3). Experiment III addressed the role of PUFA in the tumor growth modulation by vitamin E. For this purpose, we compared the effect of vitamin E in 15% fat diets containing a high level of 18:3(n-3) (linseed oil, high-PUFA diet) or devoid of 18:3(n-3) (hydrogenated palm/sunflower oil, low-PUFA diet). In Experiments I-III, tumor growth increased in the presence of vitamin E compared with control (without vitamin E). Furthermore, it decreased when prooxidant was added. In contrast, no difference was observed when the diet was low in PUFA, suggesting that sensitivity of PUFA to peroxidation may interfere with tumor growth. This observation was supported by growth kinetic parameter analysis, which indicated that tumor growth resulted from variations in cell loss but not from changes in cell proliferation. These data show that, in vivo, PUFA effects on tumor growth are highly dependent on diet oxidative status.

 

その９

Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids.

Abstract

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.

 

その１０

Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary docosahexaenoic acid

Abstract

Dietary docosahexaenoic acid (DHA), which integrates into tumor cell membranes, has been reported to enhance the efficacy against tumors of cytotoxic drugs that induce reactive oxygen species (ROS). Because ionizing radiation also generate ROS, we initiated a study to determine whether dietary DHA might sensitize mammary tumors to irradiation. Mammary tumors were induced by N‐methylnitrosourea (NMU) in Sprague‐Dawley rats. The optimal dose of radiation to examine the effect of DHA on tumor response to irradiation was determined to be 18 grays (Gy) using a 4–6 MeV electron beam (according to the depth of the target volume) delivered in a single fraction from a linear accelerator. Two groups of rats were fed a basal diet containing 7% of a mixture of peanut and rapeseed oils enriched with 8% of an oil containing either a low (palm oil) or high (DHASCO oil containing 40% DHA) DHA content. DHA group was equally subdivided into 2 groups without or with addition of vitamin E (100 IU/kg diet). Irradiation was carried out when the first tumor in each rat reached 1.5 cm2 and subsequent change in tumor size was documented over time. DHA level in adipose tissue, taken as a biomarker, was higher in the DHA supplemented group compared to the control group. Vitamin E level in liver, the best storage for this compound, was higher in the vitamin E supplemented DHA group compared to the DHA group. Tumor size decreased by 60% at 12 days after irradiation in the DHA group vs. 31% in the control group (p = 0.03) and 36% in the DHA plus vitamin E group. Therefore, dietary DHA sensitized mammary tumors to radiation. The addition of vitamin E inhibited the beneficial effect of DHA, suggesting that this effect might be mediated by oxidative damage to the peroxidizable lipids.