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The 2002 ISSFAL Meeting arranged a special evening discussion with professional dietitians about diet-tissue-disease relationships involving essential fatty acids and eicosanoids. The balance of eicosanoid precursors in human tissues differs widely, reflecting voluntary dietary choices among different groups worldwide. An empirical quantitative diet-tissue relationship fits these diverse values as well as other research reports on essential fatty acid metabolism. Information for dietitians and nutritionists about essential fatty acids and eicosanoids is also given in two distance learning web sites, and http://, which facilitate dietitian education and diet counseling. These sites also have an innovative, interactive diet planning software program with the empirical equation embedded in it to help evaluate personal food choices in the context of the diet-tissue-disease relationship and other widely recommended dietary advice.
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ABSTRACT: The 2002 ISSFAL Meeting arranged a special evening
discussion with professional dietitians about diet-tissue-disease re-
lationships involving essential fatty acids and eicosanoids. The bal-
ance of eicosanoid precursors in human tissues differs widely, re-
flecting voluntary dietary choices among different groups world-
wide. An empirical quantitative diet-tissue relationship fits these
diverse values as well as other research reports on essential fatty
acid metabolism. Information for dietitians and nutritionists about
essential fatty acids and eicosanoids is also given in two distance
learning web sites, and http://, which facilitate dietitian education and diet
counseling. These sites also have an innovative, interactive diet
planning software program with the empirical equation embedded
in it to help evaluate personal food choices in the context of the
diet-tissue-disease relationship and other widely recommended di-
etary advice.
Paper L9161 in Lipids 38, 317–321 (April 2003).
Non-steroidal anti-inflammatory drugs (NSAID) are some of the
most widely used medications worldwide. The >70–100 million
NSAID prescriptions written annually offer a huge profitability
potential with annual sales of $13 billion. The 24.5 million Cele-
prescriptions in 2001 in the United States were closely
matched by 23.7 million prescriptions for Vioxx
; these two
alone had worldwide sales of $5.7 billion. The drugs are taken
to decrease an overactive self-healing response by the body’s
autacoids (auto = self, akos = healing), the n-6 eicosanoids de-
rived from essential fatty acids obtained from the diet (1). This
review examines ways in which less costly dietary approaches
might also beneficially decrease those overactive responses. The
NSAID produce their beneficial anti-inflammatory, analgesic,
antipyretic, antithrombotic effects by inhibiting the cyclooxy-
genase enzyme that converts highly unsaturated fatty acid
(HUFA) precursors into active eicosanoids. The worldwide
success of NSAID provides ample “proof of principle” for the
desirability of preventing excessive n-6 eicosanoid formation
in many disorders such as thrombosis, the arrhythmia of heart
attacks, and inflammatory/immune problems in atherosclero-
sis, arthritis, asthma, and tumor angiogenesis. Moderating
those excesses brings an improved quality of life to millions
of people. Unfortunately, nearly all of the drugs have some
undesired side effects or limitations that are much discussed
in assessing benefits and risks of medical treatments.
Ironically, the self-healing eicosanoids that are so impor-
tant in the body’s normal adaptive processes are sometimes
overly mobilized, causing people to seek various self-admin-
istered medication to decrease the “friendly fire” of those
overresponses. The n-6 eicosanoid is formed more rapidly in
the case of prostaglandin derivatives (2,3), and acts more in-
tensely in receptor signaling (4) compared with its competing
n-3 eicosanoid analog (esp. leukotriene B chemotaxis). These
differences produce less intense actions when the mixture of
released HUFA precursors has a lower proportion of the n-6
analog to compete for the eicosanoid-forming enzymes. Phys-
iologic benefits depend on moderate transient actions of these
autacoids formed from local precursors present in nearly all
tissues of the body (1). Once formed, eicosanoids are rapidly
inactivated so that active autacoid usually appears only in
small amounts at nearby tissue receptors and travels little dis-
tance from its site of synthesis. As a result, a small increase
or decrease in the rate of synthesis causes a very important
difference in the intensity of an autacoid’s action at local re-
ceptors (1). Inhibitory drugs are voluntarily used by people to
moderate an overresponse when eicosanoid action is more in-
tense or for a longer time than desired. However, the differ-
ence in potency between the n-3 and n-6 eicosanoids gives
another opportunity to decrease chronic excessive formation
and action of n-6 eicosanoids by increased dietary intakes of
naturally occurring competitive n-3 analogs rather than with
pharmaceutical antagonists.
Dietary intake is the only route of entry for eicosanoid precur-
sors, and food choices have an important effect on tissue HUFA
levels and tissue autacoid responses. Dietary 18-carbon essen-
Copyright © 2003 by AOCS Press 317 Lipids, Vol. 38, no. 4 (2003)
*Address correspondence at 6100 Westchester Park Dr., Apt. 1219, College
Park, MD 20740. E-mail:
Abbreviations: AA, arachidonic acid; CHD, coronary heart disease; DGLA,
di-homo-γ-linolenic acid; HUFA, highly unsaturated fatty acids; MRFIT,
multiple risk factor intervention trial; NSAID, non-steroidal anti-inflamma-
tory drugs.
Diets Could Prevent Many Diseases
William E.M. Lands*
College Park, Maryland 20740
tial fatty acids are metabolized to different chain lengths [such
as the 20-carbon arachidonic acid, AA (20:4n-6), and EPA
(20:5n-3)] and stored as HUFA precursors esterified to tissue
phospholipids from which they are mobilized by phospholipase-
catalyzed hydrolysis (5). The closely related n-3 and n-6 essen-
tial fatty acids compete with each other for accumulation in tis-
sue phospholipids, a process long recognized since the descrip-
tion of competitive hyperbolic interactions for these two types
of nutrient by Mohrhauer and Holman (6,7). The voluntary food
choices that people make day by day provide diverse propor-
tions of n-6 and n-3 essential fatty acids associated with very
different proportions of n-6 HUFA among the total HUFA of
plasma phospholipids, which vary from 25 to 85% (Fig. 1).
Competition between the n-6 and n-3 fatty acids is clearly evi-
dent in the decreased proportions of n-3 HUFA (DHA and EPA)
associated with increased proportions of n-6 HUFA [AA and di-
homo-γ-linolenic acid (DGLA)] that are stored in the tissue
phospholipid HUFA.
High proportions of the n-6 precursor in the tissue HUFA that
will be released during a stimulus will give high rates of forma-
tion of n-6 eicosanoids, whereas low proportions will give low
rates of formation. In this way, the balance of n-3 and n-6 acids
in the diet influences the balance of n-3 and n-6 HUFA in tissues
and therefore the eventual balance of n-3 and n-6 eicosanoid ac-
tions in self-healing processes. CHD involves excessive n-6
eicosanoid actions in chronic and acute inflammatory processes
in vascular walls that predispose people to fatal heart attacks as
well as in the thrombosis and arrhythmia of the acute event. Be-
cause CHD is a major cause of death, many drug treatments are
marketed vigorously to meet the need to treat people and reduce
an imminent risk. Figure 2 shows that the age-adjusted risk of
CHD mortality is less when the proportion of n-6 eicosanoid
precursors in people’s tissue HUFA is lower. The wide diversity
in abscissa values for Figures 1 and 2 raises the question, “What
proportion of n-6 eicosanoid precursor is stored on the shelves
of your body’s medicine chest?” It also prompts a closer, more
quantitative look at the association between tissue HUFA and
CHD mortality.
318 W.E.M. LANDS
Lipids, Vol. 38, no. 4 (2003)
FIG. 1. Different tissue highly unsaturated fatty acid (HUFA) proportions among humans. The phospholipid fatty acids from 380 different plasma sam-
ples described in other studies from the United States [n = 293 (8)] and Japan [n = 87 (9)] were analyzed by gas chromatography. The proportions of in-
dividual n-3 HUFA decrease (A: EPA, 20:5n-3, ; B: DHA, 22:6n-3, ) as the n-6 HUFA increase [A: arachidonic acid (AA), 20:4n-6, ; B: di-homo-γ-
linolenic acid (DGLA), 20:3n-6, ].
FIG. 2. Coronary heart disease (CHD) mortality rates associated with
tissue HUFA proportions. Results from the United States, Japan, and
Greenland were discussed earlier (10,11,12) as were quintile results
from the Multiple Risk Factor Intervention Trial (MRFIT) study [(13)]
and those from Quebec Inuit (14), Quebec Cree (15), and Quebec over-
all (16). For abbreviation see Figure 1.
The Multiple Risk Factor Intervention Trial (MRFIT) was a
multimillion-dollar clinical trial in which the “Usual Care” co-
hort provided prospective longitudinal evidence that people con-
suming greater levels of n-3 HUFA had a lower relative risk of
CHD than those eating less (13). The voluntary intake of n-3
HUFA for 6258 men (expressed as percentage of food energy,
en%) had quintile means of 0.001, 0.004, 0.019, 0.063, and
0.272 en%. These relatively low intakes corresponded to pro-
portions of 83, 82, 81, 77, and 62% n-6 HUFA in overall tissue
HUFA, respectively. The 1251 men with the most n-3 HUFA in-
take had a significantly lower relative risk of CHD, 0.6 com-
pared with 1.0, 1.08, 0.91, 0.88. However, Table 1 shows that
the limited diversity among Americans in voluntary intake of
n-3 HUFA causes this significant effect to be less apparent when
all five quintiles are combined together. Predicting the likely
proportion of n-6 HUFA in tissue HUFA for each of the quin-
tiles (in column 6) and combining them with the known fraction
of deaths in each quintile (column 7) predicts values of 78% for
cases and 75% for surviving controls (column 8). Direct gas
chromatographic analysis of the HUFA in plasma phospholipids
gave good agreement with the values predicted from the dietary
data, with an average of 79% n-6 HUFA in tissue HUFA for 94
cases and 76% for 94 controls (17). The clear benefit seen for
one quintile and emphasized by Dolecek and Grandits (13)
seems less visible when combining all quintiles together as re-
ported by Simon et al. (17). Nevertheless, the latter authors con-
cluded that a 1 SD increase in n-6 DGLA (20:3n-6) was associ-
ated with an increase in CHD risk of 40%, whereas a 1 SD in-
crease in DHA (22:6n-3) was associated with a decrease in CHD
risk of 33% (17). They concluded that the decreased CHD inci-
dence may reflect decreased platelet aggregability after in-
creased dietary intake of n-3 polyunsaturated fatty acids.
Recent results from Quebec (see Fig. 2) fit closely to the
relationship observed for the MRFIT cohort as well as for the
United States, Japan, and Greenland populations:
CHD mortality = 3 × (% n-6 HUFA in tissue HUFA) – 75 [1]
Although cross-national analyses have been regarded with cau-
tion, the Quebec population of groups from the same province
of the same country (14–16) follows the same trend for tissue
HUFA influence on the likelihood of fatal CHD events. Knowl-
edge of the molecular mechanisms for n-6 eicosanoid actions in
the disease processes of inflammation, thrombosis, and arrhyth-
mia and the success of many NSAID in moderating those
processes leads inevitably to considering dietary steps to pre-
vent excessive n-6 eicosanoid actions before they occur rather
than relying only on treatment after disease processes become
evident. The strong correlation coefficient of 0.99 (r
= 0.986)
for the results in Figure 2 suggests that making dietary choices
that decrease the proportion of tissue HUFA that is n-6 HUFA
can be an effective primary prevention strategy to decrease the
risk of fatal CHD events in a population. Figure 1 shows
that many people already do. There are undoubtedly other
eicosanoid-mediated diseases for which better nutrition may pre-
vent what must otherwise be treated with drugs.
Diet choices influence the composition of HUFA in tissue
phospholipids, whose composition affects the likelihood of
phospholipase releasing n-6 eicosanoid precursors; that in
turn affects the probable intensity of n-6 eicosanoid synthesis
and action in tissues. In maintaining health and preventing
chronic diseases, the tissue is the issue. Extending the work
of Mohrhauer and Holman, we examined quantitative meta-
bolic relationships between dietary supply and the propor-
tions of n-6 and n-3 eicosanoid precursors stored in the HUFA
of tissue phospholipids. The proportion of n-6 in tissue HUFA
can be estimated by an empirical relationship (12) for the
quantitative metabolic competitions among four separate
types of essential fatty acids in the diet:
1. 18-carbon n-3 PUFA; 18:3n-3
2. 18-carbon n-6 PUFA; 18:2n-6
3. 20- and 22-carbon n-3 HUFA; 20:5; 22:5; 22:6n-3
4. 20- and 22-carbon n-6 HUFA; 20:3; 20:4; 22:4; 22:5n-6
Each of the four types contributes differently to the overall tis-
sue balance. Discussing the four types combined into a single
Lipids, Vol. 38, no. 4 (2003)
Combined Quintile Results from the MRFIT Study
12345 6 7 8
Quintile of n-3 HUFA n Deaths RR Dietary en% Estimated % n-6 HUFA 3 × 6 Cases (2–3) × 6 Controls
MRFIT #5 1251 24 0.60 0.272 62.3 1495. 76,434.
MRFIT #4 1252 35 0.88 0.063 76.8 2687. 93,428.
MRFIT #3 1251 35 0.91 0.019 80.9 2830. 98,335.
MRFIT #2 1197 39 1.08 0.004 82.4 3215. 95,447.
MRFIT #1 1307 42 1.08 0.001 82.8 3476. 104,692.
Total 6258 175 Dolecek data predict 78.3. 74.8.
Cases Controls
Simon data observed 78.7. 76.5
Results in the first five columns are from Dolecek and Grandits (13), and the proportion of n-6 HUFA in total HUFA was estimated by an empirical quantitative
metabolic relationship (12). Column 7 combines columns 3 and 6 to obtain the average estimated value for coronary heart disease cases, whereas column 8 gives
the average estimated value for survivors. Analytical results of Simon et al. (17) are also in columns 7 and 8.
Abbreviations: MRFIT, Multiple Risk Factor Intervention Trial; HUFA, highly unsaturated fatty acids; RR, relative risk; en%, percentage of food energy.
ratio of total dietary n-6/total dietary n-3, the ratio has no
clear meaning because tissue proportions of n-6 HUFA in
total HUFA result from the four separate contributions ex-
pressed as a percentage of total food energy (en%). To make
estimates with all four variables, a simple calculator is acces-
sible at to
help design general features of dietary intervention protocols.
To facilitate estimates of how different combinations of spe-
cific foods can give very different proportions in body tissues,
we developed an interactive personalized computer program that
manages U.S. Department of Agriculture information about the
essential fatty acids in 9214 different servings of food. The soft-
ware combines information concerning a person’s daily food
choices and predicts the resulting tissue HUFA proportions,
which are biomarkers for essential fatty acid intake (as noted in
Ref. 12) as well as surrogate clinical markers (as seen in Fig. 2)
that are also metabolically related to the probable intensity of an
eicosanoid response as noted above. It can be downloaded with-
out cost from Some ethnic
food choices achieve healthy tissue proportions and moderate
eicosanoid responses by containing large amounts of n-3 HUFA
(Japanese or Greenlanders), whereas some populations eat lower
amounts of the n-6 18-carbon fatty acids (Mediterranean peo-
ple). Although intake of linoleate is similar in the United States
and Japan (quintile means from 3 to 9 en%), the mean intake for
the lowest quintile of dietary n-3 HUFA in Japan (0.31, 0.46,
0.56, 0.71, 0.92 en%) is greater than the highest for the United
States (0.001, 0.003, 0.017, 0.057, 0.249), making tissue eico-
sanoid responses appreciably different for the two populations.
To help clinical investigators design diets that produce the
desired tissue HUFA balance, a simple spreadsheet was
arranged to combine the four separate dietary influences with
the empirical relationship described earlier (12) to predict the
likely long-term outcome. Illustrations of three typical ethnic
dietary combinations of essential fatty acid intakes (expressed
as en%) are in the columns at the right of Table 2. In a 2400
kcal/d diet, 266 mg of fat is 0.10 en%, and a standard 1-g fish
oil supplement is equivalent to 180 mg 22:6 + 120 mg 20:5,
i.e., ~0.11 en% n-3 HUFA per capsule.
Dietitians who know the importance of voluntary food
choices can use their familiarity with nutrient tables and the
new interactive software on essential fatty acids to help peo-
ple choose healthy combinations of palatable foods that will
fit their personal tastes and meet their personal target for the
balance of tissue HUFA. The interactive software combines
the selected foods into daily meal plans, tracking the calories
and estimating the probable proportions of n-6 HUFA in the
total tissue HUFA, which can vary from 25 to 85%. The
American Heart Association has recommended at least two
meals per week of fatty fish to help provide better tissue bal-
ance. Careful attention to raising the relative amount of n-3
to n-6 contents of salad and cooking oils is another easy step
in shifting tissue HUFA to a healthier balance. Also, discov-
ering and eating the vegetables and legumes with relatively
higher proportions of n-3 acids is made easier with a comput-
erized “sort” command. All of the above aspects open the way
for dietitians to lead in developing primary prevention strate-
gies that decrease the frequency and severity of eicosanoid-
mediated disorders for the whole population.
Support for developing the empirical quantitative metabolic diet-
tissue relationship was from a Pfizer Biomedical Research Award;
the distance learning web site (
hosted by the Office of Dietary Supplements provides the free down-
loaded interactive food choice software that was developed with
support from the National Institute on Alcohol Abuse and Alco-
holism. I thank Drs. W.S. Harris and M. Kobayashi for sharing their
detailed analytical results.
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320 W.E.M. LANDS
Lipids, Vol. 38, no. 4 (2003)
Daily Dietary Intakes Affect Tissue HUFA
Type of essential Trial
Typical diets
fatty acid in the diet diet U.S. Mediterranean Japan
1 en% 18:3n-3 1.00 0.85 0.50 0.83
2 en% 18:2n-6 6.00 6.82 2.30 5.41
3 en% n-3 HUFA 0.10 0.03 0.09 0.71
4 en% n-6 HUFA 0.10 0.08 0.08 0.09
% n-6 in total HUFA 75.10 80.10 63.10 48
For abbreviations see Table 1.10
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[Received September 23, 2002, and in revised form and accepted
April 8, 2003]
Lipids, Vol. 38, no. 4 (2003)
... The proportion of n-6 in blood HUFA (% n-6 in HUFA) is a valid biomarker for relative intakes of n-3 and n-6 nutrients (Lands and Lamoreaux, 2012;Lands et al., 1992). The % n-6 in HUFA also strongly predicts risk for CHD (Lands, 2003). It closely related to the degree with which the food energy biomarker (blood cholesterol) correlated with 25-year mortality in the Seven Countries Study (Lands, 2014). ...
... Reference values for Body Mass Index (BMI), Mid-Upper Arm Circumference (MUAC) (NIH, 2016;WebMd, 2016), total n-3 LC-PUFA content in blood, ratio of n-3 LC-PUFA to total LC-PUFA (Lands, 2003;Harris, 2007), and recommendent nutrition intake (RNI) essential micronutrients, protein, and energy were obtained from standard sources (Islam et al., 2010;INFS, 2013;UNICEF, 2013). All analyzed data, graphical presentation of data have been customized from the statistical package program R (R Core Team, 2016). ...
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... The oil's remarkable oxidative stability has long been exploited in Africa, especially for meat preservation [40]. Also, the oil in MSC contains some essential FAs (EFAs) linoleic and α-linolenic acids whose dietary incorporation into ADFs would help in the fight against human illnesses like rheumatoid arthritis [41] and diabetics [42]. Therefore, incorporation of MSC into animal diets in Southern African where this product is produced would not only supply much needed protein, energy and other nutrients, but would also enhance the shelf-life and health status of meat and other ADFs that would, consequently, improve health benefits to human consumers. ...
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Marula seed cake (MSC) is a nutritionally-rich natural feed resource that can enhance the healthiness of animal-derived foods (ADFs) for human consumption. This study compared the health-related fatty acid (FA) profiles of MSC products from South Africa and Eswatini. Composite samples monthly collected from both countries were analysed for FAs. MSC products from both countries were found to be dominated by oleic acid (>70%), followed by palmitic, linoleic and stearic acids. Consequently, both products had their FA totals dominated by ƩMUFA followed by ƩSFA, ƩPUFA, Ʃn-6 PUFA and Ʃn-3 PUFA. Both oleic and stearic acids were higher (P < 0.01) whilst linoleic (P < 0.001), α-linolenic (P < 0.05), margaric (P < 0.05), palmitoleic (P < 0.05) and eicosatrienoic (P < 0.05) acids were lower in South African in comparison to Eswatini MSC. Consequently, South African MSC had higher ƩMUFA (P < 0.01) but lower ƩPUFA (P < 0.001), Ʃn-6 PUFA (P < 0.001) and Ʃn-3 PUFA (P < 0.05). Also, Eswatini MSC had higher n-6 : n-3 PUFA, PUFA : SFA (P = 0.001) and PUFA : MUFA (P < 0.05) ratios. Further, MSC products from both countries had similarly (P > 0.05) low atherogenicity and high desaturase indices. In conclusion, both country products are rich particularly in oleic acid and their incorporation into farm animal diets would increase content of the MUFA in ADFs and, consequently, improve health benefits to human consumers.
... 145 Thus, a ratio of omega-3 to omega-6 (n-3:n-6) was suggested to represent the body's potential inflammatory response to insult. 146 As increased inflammatory states have been found to play a role in the pathophysiology of depression, 147 bipolar disorder, 148 schizophrenia, 149 and cardiovascular disorders, 147 increasing the 'good' omega-3 fatty acids and lowering the 'bad' omega-6 fatty acids could be beneficial. ...
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The American Psychiatric Association (APA) currently recommends the use of omega-3 fatty acid supplementation for depressive disorders, impulse-control disorders, and psychotic disorders in treatment guidelines. This review examines the evidence for efficacy of omega-3 fatty acids in depressive disorders, bipolar disorder, anxiety disorders, post-traumatic stress disorder (PTSD), and psychosis. Meta-analysis of randomized-controlled trials of omega-3 fatty acids for depression are inconclusive, with strong evidence of publication bias, sizable heterogeneity between included studies, and substantial methodological shortcomings in included trials. The large amount of heterogeneity in findings of RCTs of omega-3 fatty acids for unipolar depression is likely attributable to highly heterogeneous sample populations that are given different omega-3 supplements [which differ widely in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, ratio, and dosage] as either adjunctive or monotherapy of other existing treatments, and then measure several different outcomes of depression symptomatology with likely incomplete blinding. Evidence of efficacy of omega-3 supplementation in treating psychosis, PTSD, anxiety, and bipolar mania is minimal. The current guidelines recommending the use of omega-3 fatty acids in adulthood psychiatric conditions should be revisited, especially given several recent negative studies examining the effects of omega-3 fatty acids for cardiovascular disease. Recommending likely ineffective treatment to patients, no matter how benign the side-effect profile, has opportunity cost (e.g. other more effective medications or therapies not being utilized) and likely affects patient compliance with other evidence-based treatments.
This review examines lipids and lipid-binding sites on proteins in relation to cardiovascular disease. Lipid nutrition involves food energy from ingested fatty acids plus fatty acids formed from excess ingested carbohydrate and protein. Non-esterified fatty acids (NEFA) and lipoproteins have many detailed attributes not evident in their names. Recognizing attributes of lipid-protein interactions decreases unexpected outcomes. Details of double bond position and configuration interacting with protein binding sites have unexpected consequences in acyltransferase and cell replication events. Highly unsaturated fatty acids (HUFA) have n-3 and n-6 motifs with documented differences in intensity of destabilizing positive feedback loops amplifying pathophysiology. However, actions of NEFA have been neglected relative to cholesterol, which is co-produced from excess food. Native low-density lipoproteins (LDL) bind to a high-affinity cell surface receptor which poorly recognizes biologically modified LDLs. NEFA increase negative charge of LDL and decrease its processing by “normal” receptors while increasing processing by “scavenger” receptors. A positive feedback loop in the recruitment of monocytes and macrophages amplifies chronic inflammatory pathophysiology. Computer tools combine multiple components in lipid nutrition and predict balance of energy and n-3:n-6 HUFA. The tools help design and execute precise clinical nutrition monitoring that either supports or disproves expectations.
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Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring – events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of ω-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The ω-3 HUFA score, calculated as [100 × (ω-3 HUFAs/(ω-3 HUFAs + ω-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 × ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the ω-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO2-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The ω-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the ω-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO2-triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable ω-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how ω-3 HUFA consumption influences lupus and other autoimmune diseases.
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2 ‫رﺋﻮﻓﻲ‬ ‫ﺳﻮﺳﻦ‬ ‫ﺳﻴﺪه‬ ، ‫ﻛﻼﭼﺎﻳﻪ‬ 3 1. ‫ﻣﺎﻣﺎﻳﻲ،‬ ‫ﮔﺮوه‬ ‫ﻣﺎﻣﺎﻳﻲ،‬ ‫ارﺷﺪ‬ ‫ﻛﺎرﺷﻨﺎس‬ ‫ﻣﺮﺑﻲ،‬ ‫ﭘﺰﺷﻜ‬ ‫و‬ ‫ﭘﺎﻳﻪ‬ ‫ﻋﻠﻮم‬ ‫داﻧﺸﻜﺪة‬ ‫ﻲ‬ ، ‫اﺳﻼﻣﻲ،‬ ‫آزاد‬ ‫داﻧﺸﮕﺎه‬ ‫واﺣﺪ‬ ‫زﻧﺠﺎن‬-‫اﻳﺮان.‬ ‫زﻧﺠﺎن،‬ 2. ‫ﻣﺎﻣﺎﻳﻲ‬ ‫ارﺷﺪ‬ ‫ﻛﺎرﺷﻨﺎس‬ ‫ﻣﺮﺑﻲ،‬ ‫اﺳﻼﻣﻲ،‬ ‫آزاد‬ ‫داﻧﺸﮕﺎه‬ ‫ﭘﺰﺷﻜﻲ،‬ ‫و‬ ‫ﭘﺎﻳﻪ‬ ‫ﻋﻠﻮم‬ ‫داﻧﺸﻜﺪة‬ ‫ﻣﺎﻣﺎﻳﻲ،‬ ‫ﮔﺮوه‬ ، ‫واﺣﺪ‬ ‫زﻧﺠﺎن‬-‫اﻳﺮان.‬ ‫زﻧﺠﺎن،‬ 3. ‫ﭘﺮﺳﺘﺎري‬ ‫ارﺷﺪ‬ ‫ﻛﺎرﺷﻨﺎس‬ ‫ﻣﺮﺑﻲ،‬ ‫اﺳﻼﻣﻲ،‬ ‫آزاد‬ ‫داﻧﺸﮕﺎه‬ ‫ﭘﺰﺷﻜﻲ،‬ ‫و‬ ‫ﭘﺎﻳﻪ‬ ‫ﻋﻠﻮم‬ ‫داﻧﺸﻜﺪة‬ ‫ﭘﺮﺳﺘﺎري،‬ ‫ﮔﺮوه‬ ، ‫واﺣﺪ‬ ‫زﻧﺠﺎن‬-‫اﻳﺮان.‬ ‫زﻧﺠﺎن،‬ ‫درﻳﺎﻓﺖ:‬ ‫ﺗﺎرﻳﺦ‬ 03 / 04 / 93 ‫ﭘﺬﻳﺮش:‬ ‫ﺗﺎرﻳﺦ‬ 23 / 09 / 93 ‫ﭼﻜﻴﺪه‬ ‫ﻣﻘﺪﻣﻪ:‬ ‫ﻣﻴﺎن‬ ‫ﻗﺮار‬ ‫ﺗﺎﺛﻴﺮ‬ ‫ﺗﺤﺖ‬ ‫را‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﺳﺎﻟﻲ‬ ‫ﻣﻲ‬ ‫دﻫﺪ‬ ‫ﻣﻲ‬ ‫ﺳﻨﻲ‬ ‫دوره‬ ‫اﻳﻦ‬ ‫اﺻﻠﻲ‬ ‫ﺷﻜﺎﻳﺖ‬ ‫ﮔﺮﮔﺮﻓﺘﮕﻲ‬. ‫ﺑﺎﺷﺪ.‬ ‫ﺣﺎﻟﺖ‬ ‫اﻳﻦ‬ ‫ﻣﻲ‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻠﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﺑﺮ‬ ‫و‬ ‫ﻧﻤﻮده‬ ‫ﻣﺨﺘﻞ‬ ‫را‬ ‫ﺑﻮدن‬ ‫ﺳﺎﻟﻢ‬ ‫و‬ ‫ﺧﻮب‬ ‫اﺣﺴﺎس‬ ‫ﺗﻮاﻧﺪ‬ ‫ﺑﮕﺬارد.‬ ‫ﺗﺎﺛﻴﺮ‬ ‫ﻣﻜﻤﻞ‬ ‫ﺗﺎﺛﻴﺮ‬ ‫ﺑﺮرﺳﻲ‬ ‫ﻫﺪف‬ ‫ﺑﺎ‬ ‫ﻣﻄﺎﻟﻌﻪ‬ ‫اﻳﻦ‬ ‫ﺷﺪ.‬ ‫اﻧﺠﺎم‬ ‫ﻳﺎﺋﺴﻪ‬ ‫ﺳﺎل‬ ‫ﻣﻴﺎن‬ ‫زﻧﺎن‬ ‫در‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﺑﺮ‬ ‫ﻣﺎﻫﻲ‬ ‫روﻏﻦ‬ ‫روش‬ ‫و‬ ‫ﻣﻮاد‬ ‫ﻫﺎ:‬ ‫روي‬ ‫ﺑﺮ‬ ‫و‬ ‫اﺳﺖ‬ ‫ﻛﻮر‬ ‫ﺳﻮ‬ ‫دو‬ ‫ﺷﺪه‬ ‫ﺗﺼﺎدﻓﻲ‬ ‫ﺷﺎﻫﺪدار‬ ‫ﺑﺎﻟﻴﻨﻲ‬ ‫ﻛﺎرآزﻣﺎﻳﻲ‬ ‫ﻳﻚ‬ ‫ﺣﺎﺿﺮ‬ ‫ﭘﮋوﻫﺶ‬ 68 ‫ﺳﺎل‬ ‫ﻣﻴﺎن‬ ‫زن‬ ‫ﻳﺎﺋﺴﻪ‬ 45 ‫ﺗﺎ‬ 60 ‫ﺗﺼﺎدﻓﻲ‬ ‫ﺗﺨﺼﻴﺺ‬ ‫ﺻﻮرت‬ ‫ﺑﻪ‬ ‫ﻛﻪ‬ ‫ﺳﺎﻟﻪ‬ ‫ﺑﻪ‬ ‫ﮔﺮوه‬ ‫دو‬ ‫ﺑﻪ‬ ‫ﺷﺪ.‬ ‫اﻧﺠﺎم‬ ‫ﮔﺮﻓﺘﻨﺪ،‬ ‫ﻗﺮار‬ ‫داروﻧﻤﺎ‬ ‫و‬ ‫ﻣﺎﻫﻲ‬ ‫روﻏﻦ‬ ‫ﮔﺮوه‬ ‫دو‬ ‫در‬ ‫ﻣﺪت‬ 8 ‫ﻛﭙﺴﻮل‬ ‫ﻋﺪد‬ ‫ﻳﻚ‬ ‫روزي‬ ‫ﻫﻔﺘﻪ‬ 1000 ‫ﭘﺮﺳﺸﻨﺎﻣﻪ‬ ‫از‬ ‫ﻫﺎ‬ ‫داده‬ ‫آوري‬ ‫ﮔﺮد‬ ‫ﺟﻬﺖ‬ ‫ﺷﺪ.‬ ‫داده‬ ‫داروﻧﻤﺎ‬ ‫ﻳﺎ‬ ‫ﻣﺎﻫﻲ‬ ‫روﻏﻦ‬ ‫ﮔﺮﻣﻲ‬ ‫ﻣﻴﻠﻲ‬ ‫ﺟﻬ‬ ‫ﺑﻬﺪاﺷﺖ‬ ‫ﺳﺎزﻣﺎن‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﭘﺮﺳﺸﻨﺎﻣﻪ‬ ‫و‬ ‫ﻏﺬاﻳﻲ‬ ‫ﺑﺴﺎﻣﺪ‬ ‫ﭘﺮﺳﺸﻨﺎﻣﻪ‬ ‫دﻣﻮﮔﺮاﻓﻴﻚ،‬ ‫اﻃﻼﻋﺎت‬ ‫ﺎﻧﻲ‬ ‫آزﻣﻮن‬ ‫ﺑﺎ‬ ‫ﻧﺘﺎﻳﺞ‬ ‫ﮔﺮدﻳﺪ.‬ ‫اﺳﺘﻔﺎده‬ ‫ﮔﺮﻓﺖ.‬ ‫ﻗﺮار‬ ‫ﺗﺤﻠﻴﻞ‬ ‫و‬ ‫ﺗﺠﺰﻳﻪ‬ ‫ﻣﻮرد‬ ‫ﻓﺮﻳﺪﻣﻦ‬ ‫و‬ ‫وﻳﺘﻨﻲ‬ ‫ﻣﻦ‬ ‫دو،‬ ‫ﻛﺎي‬ ‫ﺗﻲ،‬ ‫آﻣﺎري‬ ‫ﻫﺎي‬ ‫ﻳﺎﻓﺘﻪ‬ ‫ﻫﺎ:‬ ‫از‬ ‫ﭘﺲ‬ ‫ﻧﺪاﺷﺘﻨﺪ.‬ ‫داري‬ ‫ﻣﻌﻨﻲ‬ ‫اﺧﺘﻼف‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﻛﻞ‬ ‫ﻧﻤﺮه‬ ‫و‬ ‫ﻏﺬاﻳﻲ‬ ‫ﻓﺮم‬ ‫دﻣﻮﮔﺮاﻓﻴﻚ،‬ ‫ﻣﺸﺨﺼﺎت‬ ‫ﻧﻈﺮ‬ ‫از‬ ‫ﮔﺮوه‬ ‫دو‬ 8 ‫ﻛ‬ ‫ﻛﻞ‬ ‫ﻧﻤﺮه‬ ‫ﻧﻈﺮ‬ ‫از‬ ‫ﮔﺮوه‬ ‫دو‬ ‫ﺑﻴﻦ‬ ‫ﻣﺪاﺧﻠﻪ،‬ ‫ﻫﻔﺘﻪ‬ ‫ﻛﻨﻨﺪه‬ ‫ﻣﺼﺮف‬ ‫ﮔﺮوه‬ ‫در‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫و‬ ‫ﺷﺪ‬ ‫اﻳﺠﺎد‬ ‫دار‬ ‫ﻣﻌﻨﻲ‬ ‫اﺧﺘﻼف‬ ‫زﻧﺪﮔﻲ‬ ‫ﻴﻔﻴﺖ‬) ‫ﻳﺎﻓﺖ‬ ‫ﺑﻬﺒﻮد‬ ‫داروﻧﻤﺎ‬ ‫ﮔﺮوه‬ ‫ﺑﺎ‬ ‫ﻣﻘﺎﻳﺴﻪ‬ ‫در‬ ‫ﻣﺎﻫﻲ‬ ‫روﻏﻦ‬ 001 / 0 > p .(‫ﻧﺘﻴﺠﻪ‬ ‫ﮔﻴﺮي‬ : ‫ﻣﺎﻫﻲ‬ ‫روﻏﻦ‬ ‫ﻞ‬ ‫ﻣﻜﻤ‬ ‫ﺑﺎ‬ ‫درﻣﺎن‬ ‫ﻣﻲ‬ ، ‫ﻣﻴﺎن‬ ‫زﻧﺎن‬ ‫در‬ ‫را‬ ‫زﻧﺪﮔﻲ‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﺗﻮاﻧﺪ‬ ‫ﺑﺨﺸﺪ.‬ ‫ﺑﻬﺒﻮد‬ ‫ﻳﺎﺋﺴﻪ‬ ‫ﺳﺎل‬ ‫ﻛﻠﻴﺪواژه‬ ‫ﻫﺎ:‬ ‫ﻛﻴﻔﻴﺖ‬ ‫ﻣﺎﻫﻲ،‬ ‫روﻏﻦ‬ ‫ﻣﻴﺎن‬ ‫زﻧﺎن‬ ‫زﻧﺪﮔﻲ،‬ ‫ﻳﺎﺋﺴﻪ.‬ ‫ﺳﺎل‬
Krill oil (KO) is unique in contrast to fish oil because the ω-3 PUFAs, particularly eicosapentaenoic (EPA) and docosahexaenoic (DHA), are almost exclusively esterified on phospholipids (PL) rather than triglycerides (TAG) which improves bioavailability and water solubility. Therefore, the primary aim of this study was to use the principles of water degumming to separate PL from TAG in KO. Water was mixed with KO in varying ratios, centrifuged for separation and freeze-dried. Separation into gum and oil fractions occurred in the 75:25 and 50:50 KO:H2O samples. TLC-densitometry revealed 67.6 ± 1.97% and 49.73 ± 3.90% PL concentrations (p < 0.05) in the lipid recovered from the 75:25 and 50:50 KO:H2O sample, respectively. The 75:25 KO:H2O gum fraction did not contain detectable triglycerides (TAG); however, the 50:50 KO:H2O gum fraction had 23.88 ± 6.36% (p < 0.05). The fatty acid profile of the 75:25 KO:H2O gum fractions presented with more EPA and DHA than the oil fraction (p < 0.05). Phosphatidylcholine (PC) with EPA and DHA fatty acids attached concurrently at sn-1 and sn-2 (i.e., PC-EPA/EPA, PC-EPA/DHA, and PC-DHA/DHA) and was present in the gum fractions of both samples. This approach offers a simple separation technique to separate health-beneficial PL from KO.
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Previously traditional dietary patterns in Japan are no longer typical. The current changing conditions provide an opportunity to examine more closely some important health conditions associated with the changed lifestyle and concentrations of dietary total fat and saturated fatty acid, and the ratio of n-3 to n-6 polyunsaturated fatty acids in the diet.
Background: Canadian native populations, which traditionally consume large amounts of fish, have lower rates of mortality from heart disease than do Canadian nonnative populations, which have low fish intakes. Fish oils rich in n−3 fatty acids may have a protective effect against cardiovascular disease (CVD) risk factors. Objectives: The purposes were to examine the profile of plasma phospholipid concentrations of the n−3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) among James Bay Cree and to verify the relation between these concentrations and CVD risk factors. Design: The study population consisted of 917 subjects aged 18–74 y who participated in the 1991 Santé Québec Health Survey. Data were obtained through home interviews and clinic visits. Plasma samples were analyzed for phospholipid fatty acid composition. Results: The mean fish consumption on the day before the survey was 60 g among the adult Cree population. Expressed as a percentage of total fatty acids, relative concentrations of EPA and DHA were 0.65% and 2.80%, respectively. n−3 Fatty acids were higher among coastal residents than among inland residents. A positive association was observed between plasma HDL and n−3 fatty acids. EPA and EPA+DHA were inversely associated with triacylglycerols. Among subjects aged 50–74 y, an inverse association between EPA and EPA:AA and total:HDL cholesterol was observed. Conclusions: n−3 Fatty acids may favorably influence some CVD risk factors. The Cree population must be encouraged to maintain their traditional fish-based diet, which may be one of the factors protecting them against mortality from CVD.
Highly purified cyclooxygenase from sheep vesicular glands is stimulated by the presence of protoporphyrin IX compounds. This stimulation may be due to the conversion of an apoenzyme to the holoenzyme, and full activity is achieved when half of the enzyme subunits (70,000 daltons) bind heme. Also, one-half of the subunits appear to contain non-heme iron. The apparent molecular weight of the holoenzyme is approximately 300,000 daltons and is compatible with a complex of four 70,000 dalton subunits. Thus, we suggest that heme and non-heme iron may be attached to different 70,000 daltons subunits that make up an A2B2-type of peptide chain arrangement.
Prostaglandin NomenclatureNature, Location and Distribution of the Prostaglandin Biosynthetic EnzymesNature and Origin of Fatty Acid Substrates for the CyclooxygenaseChemical Transformations Catalysed by the CyclooxygenaseTissue DamagePharmacological Control of Lipid Mediator ProductionSummary and Conclusions DiscussionReferences
Platelets enzymatically convert prostaglandin H3 (PGH3) into thromboxane A3. Both PGH2 and thromboxane A2 aggregate human platelet-rich plasma. In contrast, PGH3 and thromboxane A3 do not. PGH3 and thromboxane A3 increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A2 activity or events leading to its activation. PGI3 (Δ17-prostacyclin; synthesized from PGH3 by blood vessel enzyme) and PGI2 (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH3, thromboxane A3, and PGI3, are capable of interfering with aggregation of platelets in platelet-rich plasma.
With improved techniques for isolation and identification of materials, thromboxane (TXA2) and prostacyclin (PGI2) derivatives are now recognized as more abundant in some tissues and more potent than PGE2 and PGF2alpha. The rapid appearance and disappearance of these autacoids can be regulated at many points along the enzymatic path. Two important features affecting the rate of overall prostaglandin formation are the availability of non-esterified substrate and the availability of hydroperoxide activator for the cyclooxygenase. The fate of the endoperoxide formed by this reaction then depends upon the different relative amounts of the synthases and dehydrogenases in each type of synthesizing cell. Important future developments will indicate ways in which the amounts of these enzyme activities are altered and the ways in which the prostaglandin receptors interact with cellular adenyl cyclase and adrenergic receptors.
Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 (n - 6) and 18:3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3) fatty acid in decreasing the ability of dietary 18:2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.
Highly purified cyclooxygenase from sheep vesicular glands is stimulated by the presence of protoporphyrin IX compounds. This stimulation may be due to the conversion of an apoenzyme to the holoenzyme, and full activity is achieved when half of the enzyme subunits (70,000 daltons) bind heme. Also, one-half of the subunits appear to contain non-heme iron. The apparent molecular weight of the holoenzyme is approximately 300,000 daltons and is compatible with a complex of four 70,000 dalton subunits. Thus, we suggest that heme and non-heme iron may be attached to different 70,000 daltons subunits that make up an A2B2-type of peptide chain arrangement.
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