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Abstract: A new global analysis of all relevant population research found shows that certain omega-3 polyunsaturated fats called EPA and DHA found in fish and fish oils and another named Alpha Linolenic Acid found in a variety of foods can reduce the risk of death from cardiovascular diseases about in half. This target will require intakes of about 400 mg/day of EPA+DHA or 1500 mg/day of Linolenic acid respectively, or combinations of these nutrients in lesser amounts individually. Life Ahead provides the tools needed to identify how much of each of these key nutrient fats are included in a diet, and how needed amounts of them can be obtained by specific diet modifications or from available dietary supplements. A typical US person of age 50 will be able to achieve a gain of about 1.5 to 2 years of future Well-Days by conveniently improving usual intake of omega-3 acids over future years. Those with very low present intakes have an opportunity to gain 3 or more years from this diet modification.

Background: We have been barraged for decades by advice to eat less fat. "The cry has been "Keep your fat down to 30% of calories" This is wrong. The Eskimos that ate by he largest amount of population total fat experienced little if any heart disease. The "bad" fats are the saturated fat and transfats that usually comprises about 13% and 1% respectively of our food calories. Monounsaturated fats that account for another 13% of calories are modestly beneficial, and polyunsaturated fats that usually account for 8-9 % of our calories can be very beneficial. Thus the majority of fats are good for us And by far the most healthful of known fats are polyunsaturated ones called the omega-3's. The Eskimos ate large amounts of those omega'3's. This more than overcame the negatives of their saturated fat. Fats with 9 calories per gram do contribute to weight gain. But recent research reviewed in Life Ahead now shows that a gram of carbohydrate contributes nearly as much to weight as does a gram of fat.

There has been much publicity about omega-3 fats, more than a thousands research studies about it are posted on the NIH Medline site and books have been written about it. Yet no practical and useful way has been available for individuals to learn how much of these fats are in their usual diets, how their intake of the omega-3's compares with the amounts needed for best health, and how they can obtain most acceptably the most healthful amounts of Omega-3's. Life Ahead solves this and provides the advice needed for users to obtain the amounts needed in a variety of convenient ways.

The Omega-3's and their Unique Benefits: The first omega-3 is alpha linolenic acid, often designated 18n-3; the second is eicosapentaenoic acid, designated 20:5n-3 and called EPA; and the third is docosahexaenoic acid designated. 22:6n-3 called DHA. Linolenic acid (not to be confused with similar sounding linoleic acid) is found in flaxseed and walnut oils and a variety of foods. The EPA and DHA that are the most potently beneficial of these fats are found almost entirely and only in fish or fish oils. Our dietary intake of omega-3's must be valued based on a total of linolenic acid plus the EPA and DHA. But we can't use the usual method of just adding amounts of each because linolenic provides lesser benefits per gram of intake than does EPA and DHA.

Omega-3's provide benefits from a different that usual mechanism. First, they may not reduce the risk of heart disease per se very much. But when this event does happen, either at a first or subsequent attack, they substantially reduce the risk of all-important sudden death from the event. This is because they reduce the risk of heart arrhythmias or wildly fluctuating heart rates during an attack that can become deadly. The reduction of atherosclerosis or blood clotting that is accomplished by most other health actions does not provide this added specific benefit. Only omega-3 fatty acids and cardiofitness appear to reduce substantially the risk of sudden heart death during an attack. For this reason the omega-3 fats can substantially reduce the risk of death from a new attack for those that recovered from a prior attack. And they thus provide a benefit that is different from and adds to the benefit of most other actions that reduce the risk of an early death from a cardiovascular disease. A three fold higher amount of omega-3 linolenic was the key difference in the famous Mediterranean diet that produced a 70% lower risk of heart disease death for individuals that had the same cholesterol level. More on this follows.

Second, the health benefits of EPA and DHA are obtained coincident with or soon after their use. Reductions in risk from use of antioxidants via atherosclerosis from most vitamins act by slowing the progress of diseases, and a new use of such agents in diet requires 7-10 years of use duration for useful benefit. Third, research confirms directly that dietary supplements can provide benefits similar to those obtainable from foods.

The paragraphs that follow first pertain to EPA and DHA that usually are considered together. Analysis of the benefits of alpha linolenic acid and the way in which Life Ahead values overall Omega-3 benefits will be described following this.

The Research on Omega-3 or n-3 Fatty Acids: The section appended entitled "The Research on Health Benefits of Omega-3's---" discusses the key available research on these factors that is detailed in Tables A, B, and C. Included in this review is a tabulation of actual results now published on the benefits of eating fish. No similar comprehensive listing, review and analysis of the actual results of the overall population research on Omega-3's was found elsewhere.

A data base of 54 comparisons of the risk of different amounts fish and EPA+DHA was established from the research shown in Table A. This quite extensive data base was subjected to detailed analyses. The amounts of EPA+DHA included in each study were provided differently in various studies, but were converted to a more consistent grams and milligrams taken per day. This provides a far more potentially accurate and comprehensive analysis than that obtainable from the usual comments on results from individual studies that is provided in conventional published medical reviews.

A first finding from the analysis was that risk of disease was not related directly to amounts of EPA+DHA taken. Nearly all of the studies cited benefits for this or fish taken as infrequently as once or twice per month. Although individual studies lacked the resolving power to identify accurately the effect of amount or dose on risk, the accumulated data base of all studies showed with good significance that risk was reduced by about the 0.5 power of the amount of fish or nutrient taken. This means that it takes 4 times as much EPA+DHA to obtain a two-fold reduction in risk of (CV) disease death. This explains why quite small amounts of the nutrient could reduce risk. Some other health benefits derive in this way. For example, the risk of cigarette smoking develops as the same 0.5 power or square root of number of cigarettes smoked.

Another valuable finding from this analysis was that the EPA+DHA content of fish provides most of its health benefit. This was derived from the benefit vs. dose formulas from all research on fish and its assumed average content of EPA+DHA and from the benefit of EPA+DHA per se from observation and clinical studies. Some formulas obtained are provided following Table C. Other nutrient values of fish including its low saturated fat and antioxidants as selenium and vitamin A explain some additional heart risk benefit for fish that is now computed in Life Ahead. A value of about 0.4 gram or 400 milligrams of EPA+DHA per day reduces risk of a cardiovascular death about in half. Lower values convey higher than usually expected benefits because of the above described 0.5 power vs. amount vs. benefit. Because of the 0.5 power dose relationship quite low intakes of EPA+DHA still can provide useful benefits. For example, an intake of 200 mg per day reduces risk to 0.6 or 40%; and an intake of only 100 mg per day should reduce risk to 0.7 or 30%.

Forty two comparisons of risk from 12 research studies measured the effect of eating fish on CVD risk. Despite a failure of one study to find an effect, the resulting correlation was overwhelmingly significant with a correlation coefficient of 0.90. The coefficient 't' value of 12 noted in the appended formula is six time the value of 2 needed for 95% significance. Yet despite this impressive relationship the risk associated with different kinds of fish varies considerably. This is because the as shown in this accompanying table amount of EPA and DHA in different kinds of fish vary.

The so-called fatty fish of salmon, mackeral and herring can have up to 10 times the amount of these key nutrients as will more frequently eaten tuna, shrimp or cod. Study A57 confirms directly the substantially different changes in risk from eating fatty vs. lean fish. And there can be significant variations in the EPA+DHA content of samples of the same kind of fish. For example halibut from the Atlantic and Pacific oceans averaged 0.46%, but halibut from colder Greenland waters was 1.17% EPA+DHA.

The important observation here is that assuming that EPA+DHA is the main health benefit of fish consumption, one portion of salmon should convey the same benefit as 7 portions of cod, catfish or flounder. This is confirmed in study A57, and is further confirmed by the similar effects of EPA+DHA in supplements with that in fish. Another very important observation is that fried fish may be of no or negative benefit. This derives first from the fact that most fried fish is of the flounder or cod type that has low EPA+DHA. Further, fried fish includes more saturated fats and transfats that are known to be harmful. A direct confirmation that fried fish probably will not produce health benefits comes from study A61. Fried fish at 3+ times per week including fish sandwiches produced elevated risk ratios of 1.37, 1.64 and 1.93 for all CHD death, arrhythmic death, and non-fatal death. This compares with beneficial risks of 0.47, 0.32 and 0.67 for "Other" or not fried fish on the same population.

Recent medical advice suggests "That we should eat fish, preferably fatty fish, twice each week" Although useful, this advice now is inadequate. The substantial portion of fish eaten fried and in sandwiches could be of negative rather than positive value. And how many people know which kinds of fish are fatty? There is no guidance in this recommendation on the value of different kinds of fish or of fish supplements. There also is no advice here that Omega-3's may be provided alternatively by Linolenic acid present in many other foods.

The Life Ahead Valuation of Cardiovascular Risks for Fish and EPA+DHA. Life Ahead now values the health benefits of fish supplements and three different classes of fish as fried, not fried and lean, and salmon and fatty. Fried fish are accorded no benefits for included EPA+DHA, and are valued on their other nutrient content. The table following provides presently estimated risk ratios for CV disease death for varying amounts of these classes: Risks as for all others in Life Ahead are taken vs. that for the US average population. This assumes an average population consumption of 12.8 grams per day of fish of average 0.5 % content by weight or about 65 daily milligrams of DHA+EPA . A limiting benefit for any amount of this nutrient is set as a risk factor of 0.5 based an available research and

Risk ratio of Cardiovascular death vs. that of average US population
Portions Taken	Lean Broiled Fish	Salmon as Fatty Fish	360 mg EPA+DHA as Supplement
None	1.22	1.22	1.22
1/month	1.09	1.18	1.07
2/month	1.04	0.88	1.02
1/week	0.97	0.76	0.95
2/week	0.88	0.64	0.85
3/week	0.82	0.61*	0.76
7/week	0.66	0.61*	0.61
EPA+DHA assumed at 0.50 of the 1.22 risk or 0.61

some conservatism. This will require about 0.4 gram or 400 milligrams of EPA+DHA per day. This in turn will require two 3 ounce portions of salmon each week or a daily consumption of either a usual fish oil supplement or three ounces of a usual lean type fish. But as will be shown later, the needed intake of omega fats also can be achieved via intake of fish oil supplements or from linolenic acid. These values are for a hypothetical average person. Small women would need less, and large men would need correspondingly more of these nutrients for these estimated health benefits.

These are quite substantial benefits for an individual food, and are far larger than those obtainable from other "Good" foods such as fruits or vegetables. For example, 1 portion per week of salmon may contribute the cardiovascular risk benefits obtainable from 4 portions per day of fruits or vegetables. Eating salmon only 1 to 2 times per month appears to contribute usefully to reducing risk Computed as a single added factor, 2 portions of salmon per

day over rest of life may contribute 3 more years of average population Well-Days for a person of age 50. Although this contribution would be less when accomplished as a part of several or more other health improvements, every health-interested person should achieve a near target intake of omega-3 fatty acids. This is because these nutrients provides unique short and long term reductions in risk of major disease that may not be achievable from any other diet or health modification.

About Mercury and PCB's in Fish: There has been much publicity about the possibly harmful effect of mercury that can be included as a contaminant in fish, and especially in fresh water fish and some farmed salmon. Those at most risk appear to be young children and pregnant women. This has discouraged some people from eating any fish. The fish eaten in studies A30 through A39 conducted in various parts of the world and that probably included the usual amounts of mercury and PCB's other contaminants showed very substantial health benefits both to CV and all cause death. Thus unless there is some specific knowledge that fish available has an extraordinarily high content of mercury, the benefits of fish should vastly outweigh any negatives from included mercury. Study A38 investigated the potential harm of a rather high amount of mercury. Taken by itself, highest blood contents of mercury doubled risk of heart disease death. But the fish involved that included the most mercury still were healthful. They would have even been more healthful if the included mercury was removed. This suggests that fish should nearly always be beneficial, but that if they could be made mercury free they would be somewhat more beneficial than is now confirmed by research. A FDA advisory said the women pregnant or with young children should not eat more than 7 ounces per week of "High mercury fish" of 0.7-1 part per million. No harm was indicated for adult consumption of usual fish that has 0.05 to 0.2 parts per million of mercury. Fish now purchased commercially in stores, restaurants, etc usually is regulated for mercury content.

Similarly, much publicity has been given the possibility that sport and other fish from fresh waters and farmed salmon can contain some harmful PCB's. A review of the literature on this found no quantified evidence that harm of this could be of significance vs. the very powerful benefits of small amounts of salmon that can reduce risk of death from the major CV diseases in half. The risks of a CVD disease death for the average male US population of age 50 just to ages 60 and 70 is about 4.5% and 17% respectively. Reducing this risk in half would save 2,250 and 8,500 lives per 100,000 men. In contrast, risks of death from PCB's and most other environmental chemicals are commonly reported as a handful deaths per 100,000 individuals for lifetime exposures. It will require only two three ounce portions of salmon per week to achieve this benefit, and more salmon than this may not produce much further benefit. Thus for those concerned, there appears to little reason to eat more salmon than this for the purpose of health.. As a precaution it is best to eat fish of differing types and sources. And fish oils appear to have no mercury, PCB's or other known problem agents. Thus those concerned and those that do not like fish have this equally healthful alternative. And the publicity about mercury and PCB's has stimulated the fish industry to take serious steps to remove these problems that are in progress..

Alpha Linolenic Acid: The third important omega-3 fat is Alpha Linolenic Acid. This fat is not included in useful amounts in most fish, but derives in small individual amounts from a wide variety of foods. It is found in appreciable amounts only from flaxseed (23% by weight), butternuts(9%), walnuts(3-7%), and soybeans(2-3%). It is further included in amounts of a few tenths of a percent in each of a diverse variety of foods. It also is included in good amounts in canola or rapeseed oil, but because of recent controversy about its other possible harmful health effects the option of using canola oil is not valued in Life Ahead.

Observation studies A13, A15, A16, A19, A20 and Clinical studies A34, A39, and B1 in Tables A and B include the major available research on coronary (CHD) or cardiovascular risk. These confirm in aggregate a highly significant effect of Linolenic acid on risk of fatal heart disease. Results from large study A13 for women and from large A15 on both men and women were dose related and confirmed that largest amounts of dietary linolenic reduced risk of CHD about in half. This was confirmed further in A20 and by risks related to amounts in blood in A19, A34 and A39. Study A19 that involved strong confounding with other fats found no effect when unadjusted, but a substantial benefit after adjustment. Study A19 involved both a very high error margin and a small difference in amounts of linolenic. Recognizing this, the A19 result was statistically consistent with results of the majority.

A best quantification of the benefit of linolenic acid was derived by specialized regression of a data base of 17 risk ratios from studies A13, A15, and A20. The formula derived that is used in Life Ahead is appended following the tables. A problem in the analysis is that the methods for measuring dietary linolenic acid probably were not consistent in the different studies. Amounts of linolenic reported on average and for groups were lower in A15 than in A13 and A20. But the relationship of relative amounts to risk were still quite consistent. Many foods include small amounts of linolenic acid and derivation of a total amount in a diet is complex. The formula used herein should be reasonably consistent with the valuation method for amounts of Linolenic acid used in the Life Ahead food library.

The effects of linolenic acid differ somewhat from that of EPA+DHA. First, one gram of linolenic produces the benefit of about 1/2 gram of the more powerfully effective EPA+DHA. There is no confirmation that very small amounts of Linolenic will be beneficial as is true for EPA+DHA, and the normal first order dose relationship with log risk appears appropriate. Linolenic also appears to have a selective effect in reducing death from CHD, but less so than is true for EPA+DHA. Linolenic reduces non-fatal CHD quite usefully. No useful research was found for combinations of EPA+DHA and linolenic. But these three Omega-3 factors probably are alternates for reducing the same basic risk. Thus they should be viewed in combination.

As for all other Life Ahead risks, a risk value of 1.0 is taken for the average US population risk This includes about 65 milligrams of EPA+DHA intake per day, and about 0.7 grams of linolenic intake per day. The risks from each factor are combined. But the total risk is limited to that actually measured as a risk reduction from unity to 0.45. A maximum benefit at zero DHA+EPA intake will require a dietary intake of about 1.6 grams or 1600 mg per day of Linolenic acid, or 1.1 grams per day above the minimum of 0.5 gram/day now assumed for highest risk. The healthful targets for Life Ahead are set at 500 equivalent mg/day of DHA+EPA with Linolenic added to DHA+EPA and valued at 1/2 mg of EPA+DHA equivalent for each mg/day of Linolenic that is above the minimum base value of 500 mg/day. This value target is further adjusted for user sex and weight. It will be best achieve the target from consumption of both fish and Linolenic equivalents.

This method should provide a conservative valuation of the benefits of omega-3's. With this approach, a risk estimated from EPA+DHA will be reduced further if linolenic intake is above the population average. And risk can be reduced adequately either by adequate intake of EPA+DHA or of linolenic taken separately. But because of the lack now of confirming data, the program now limits a risk reduction for any amount or combination of omega-3's to 0.45 of that for minimal intake of each. Because of inadequate support from the research on dose relationships no increased risk is acknowledged for amounts of linolenic less that 0.5 grams or 500 mg per day as presently measured.

Yet even with this conservative approach a diet containing target amounts of omega-3's taken over life should add about 1.5 to 2 years of Well-Days to the healthy longevity of an average US 50 year old man or woman. Larger benefits are potential for those whose regular diets are now quite low in omega-3 fats. The Life Ahead diet analysis will show the potential gains in Well-Days for omega-3 dietary modifications from any present diet and combination of other factors.

The table following shows the values of Linolenic acid in grams and in equivalent milligrams of DHA+EPA for these included foods. Note that these values refer to amounts per portion of food as identified by in the Life Ahead food library, and are not the usual values per gram of weight. These values all are taken from US Dept of Agriculture data on food composition. A value equivalent of 1 gram of linolenic acid is taken as that of 0.54 grams of EPA+DHA. For comparison, a 3oz portion or 85 grams of whitefish as flounder will add about 170 mg equiv of EPA+DHA. A similar portion of salmon will add about 1250 mg and 3oz of shrimp will add 300 mg equivalents of these omega-3's. Thus for those that do not like fish, an ounce of walnuts or a teaspoon (1/3 of tablespoon) of flaxseed oil may supply the equivalent of a portion of salmon. Life Ahead now includes omega-3 values of the following listed foods.

Food	Linolenic per portion, gms / mg DHA+EPA	Food	Linolenic per portion, gms / mg DHA+EPA	Food	Linolenic per portion, gms / mg DHA+EPA	Food	Linolenic per portion, gms / mg DHA+EPA
flaxseed oil, tblsp	7.25 / 3900	potato salad,1/2 cup	0.30 / 160	milk, 3.5%, 8 oz	0.20 / 110	soybeans, 1/2 cup	0.14 / 75
walnuts, 1 oz	2.6 / 1400	mayonnaise, 1 tblsp	0.29 / 150	cheeseburger,1 med	0.20 / 110	navy beans, 1/2 cup	0.14 / 75
walnut oil, 1 tblsp	1.4 / 750	pie, 1 slice	0.25 / 135	frankfurter, 1	0.17 / 90	melon, 1/2	0.125 / 68
bean soup, 1 cup	0.50 / 270	margarine,1 tblsp	0.20 / 110	ice cream, 1/2 cup	0.15 / 80	quinoa, 1/2 cup	0.11 / 60
tuna salad, 3oz	0.50 / 270	Italian dressing, 1 tblsp	0.20 / 110	chicken dark, 3oz	0.15 / 80	olive oil, 1 tblsp	0.11 / 60
blue cheese, 1 tblsp	0.50 / 270	lamb, 3oz	0.20 / 110	cheese omelet, 5 oz	0.15 / 80	cheese, 1 oz	0.10 / 55

A rich source of linolenic acid is flaxseed oil. The seeds per se can be useful if ground adequately, but no good basis for computing effective omega-3 amounts of these was found. Walnuts and walnut oil is a next highest content source. But a variety of other foods such as bean soup, tuna salad and blue cheese can include quite useful amounts of linolenic acid. There is no way for individuals to know which foods include this nutrient and which foods do not include it in useful amounts. Life Ahead estimates an average population intake of 0.6 gram linolenic or 350 milligrams of omega-3 equivalent of DHA+EPA per day from foods other than the flaxseed oil and walnuts listed above. But the amount of linolenic in these above 'other' foods varies from 0.2 grams to 1.17 grams in the 11 Life Ahead demo diets provided in the program. Thus without a computer program such as Life Ahead there is no practical way an individual - and this includes the health professional - to know how much omega-3's are included in a diet.

There also is no relationship between omega-3 content and the usual "Good" and "Bad" health valuations of food health based only on total or saturated fat. When recognizing the contribution of its omega-3 together with other fat content, blue cheese computes as a quite healthful food. Interestingly 3.5% whole milk long thought to less healthful than than reduced fat milk turns out to be somewhat more healthful because of its omega-3 content (although it does add more calories). Reducing the milk fat even to 2% removes the omega-3's. But if adequate omega-3's are provided from other sources, these health values for milk types can reverse. Life Ahead's multivariable valuation of health benefits shows here and elsewhere that conventional health value ideas of a food that are based only on saturated fat and cholesterol can be completely wrong.

The occasional taking of a teaspoon of flaxseed oil or the eating of an ounce of walnuts could supply much of the daily need for omega-3 intake. But it may be best to obtain omega-3 intake from a combination of foods that include some fatty fish such as salmon. For example, one portion of salmon per week plus some walnuts mixed in with an ounce of nuts each evening could be a very acceptable method of obtaining what may be a very significant improvement in future health.

Life Ahead users will obtain a valuation in the diet analysis display of how much overall omega-3's are included in any diet entered, and how much more of this nutrient is needed for best health. The user then can try alternate additions of omega-3 containing foods with guidance of the above table (and these values are provided in the program) to learn how this deficiency can be acceptably corrected. The most efficient method may be to take a tablespoon of the exceptionally rich flaxseed oil just once a week, preferably with something else to mask the taste, or to take much smaller amounts of this each day in combination with some taste masking drink. Note that a tablespoon includes about 13 grams or 13,000 milligrams, and thus a portion of 1/13 or 0.076 must be entered for one usual 1000 milligram or 1 gram of flaxseed oil supplement. But as above, walnuts may provide the added nutrient needed. But some and especially those that like fish may find they are obtaining sufficient omega-3's in there present diets.

Life Ahead Explains the Mediterranean Diet: An ultimate objective of Life Ahead is to provide a model that successfully forecasts quantitatively the results of all population research of wellness factors within their margins of error. A challenge has been that of explaining the remarkable results of the so-called Mediterranean Diet. This reduced deaths of coronary disease patients by about 70% vs. a control diet that produced the same serum cholesterol. A most evident difference in this now classic research (Lorgeril, M, Lancet 1994; 343:1454 and Renaud, S; Am J Clin Nutr 1995;61S:1360S) was a three fold higher amount of linolenic acid in the experimental group. But to this date, no really clear independent evidence appears to have been provided that this change in Linolenic acid could produce such a benefit.

A customized version of Life Ahead was set up to forecast results of the control and experimental group in this study. The key difference was intake of 0.67 grams/day vs 1.79 grams/day of alpha linolenic acid in the two groups. But differences of 11.8% and 8.3% in saturated fat and in Vitamin C and carotene also contributed. Life Ahead forecasts a cardiovascular risk benefit of 61% for the experimental group vs. the control group. This compares with the measured benefit of 73% (95% range 41%-88%). Of the 61% forecast value of benefit only 6% was due to saturated fat and cholesterol, and 3% was attributable to vitamin antioxidants. This confirms that the difference in linolenic acids - as long suspected - was mostly responsible for the outstanding result of this diet. And it confirms further to every health-interested person the importance of taking adequate omega-3 fats. The Life ahead regular version as described above now provides a quite conservative valuation of the effect of these key nutrients. A memo that describes this Mediterranean diet comparison can be sent to those interested.

Omega-3's and Cancer: A few studies have examined the risk of alpha linolenic acid levels in the blood and cancer. Results suggest that the nutrient may increase the risk of prostate cancer but decrease the risk of breast cancer. At this time the evidence is not adequate to support a factor for risk of cancer for alpha linolenic acid in Life Ahead. And a present man's risk of heart disease is many times larger that of prostate cancer. But users and particularly men should not use much more than the amounts of omega-3's recommended here. Publicity about the benefits of flaxseed oil probably has motivated some users to use vastly more of this than is useful. And each extra tablespoon of this oil adds another 120 calories to a diet.

Supplements of EPA+DHA: As mentioned, research on the benefits of fish oil supplements as in studies A32, A36 and A37 showed benefits similar to those from amounts of EPA+DHA in fish. Thus those that find fish distasteful have the option of using fish supplements which have a benign taste. A popular fish oil supplement of 1.2 grams includes 216 mg of EPA and 144 mg of DHA, or a total of 360 mg or 0.36 gram of the needed nutrients. But other supplements may include differing amounts of EPA and DHA. Thus Life Ahead provides for entering the actual average amount of EPA+DHA taken per day in milligrams from a supplement. The program values omega-3 factors from fish as the sum of the average amount of EPA+DHA eaten in fish intake plus that eaten in supplements per day. And omega-3 benefits also are obtainable from the added intake of alpha linolenic acid that can be taken via supplements of flax oil.

Fish, EPA+DHA and Stroke: Studies C1 and C10-12 in Table 1 show risks of stroke for both fish intake and omega-3 fatty acid intake. On average, highest amounts of omega-3 fats reduced risk of stroke by about 25%. Although this is a somewhat lower reduction in risk than that obtained for coronary disease death, it seems likely the benefits of fish intake are roughly similar for the two different cardiovascular diseases.

Other Polyunsaturated Fats: Although the omega-3 fats are the most beneficial of the polyunsaturated fats, the full range of polyunsaturated fats appears to be somewhat more beneficial than that estimated from their effect on serum cholesterol. The Life Ahead provides a modest further benefit to all other dietary polyunsaturated fats. This is included in the formulas following the Table C.

Effect of Polyunsaturated Fats on Death from All Causes: The research in Table C following shows a consistent benefit of the included polyunsaturated fats and particularly fish and EPA+DHA on the risks of death from all causes. This provides a positive confirmation of about a 25% potential risk of death and a confirmed probable increase in life expectancy from the appropriate inclusion of these key factors in our diet.

THE RESEARCH on HEALTH BENEFITS of OMEGA-s FATTY ACIDS

The Research on Omega-3 Fats, EPA+DHA. Conventional health factor reviews usually discuss results of each individual research study, and these results taken individually nearly always are inconsistent and confusing. This is usually because individual studies can have very large margins of errors that usually are overlooked in this type of review. Life Ahead reanalyzes the actual data provided in each and all studies found objectively and more quantitatively. The Tables 1 to 3 appended here summarize actual risk values and their error margins for all useful studies found. Research on EPA and DHA that considered the benefits of the sum of these two nutrients is shown for observation studies A10-A14 and A17-20 and for clinical studies A31-2 and A36-9 are shown in Table A following. 16 of the 18 different comparisons confirmed reduced risk of CHD or CVD death for the Omega-3's. These reductions in risk often were substantial. It has been suggested that the failure of multivariable comparison A10 could have been due to the fact that most men were fish consumers and omega's were estimated from fish consumption. The comparison of those eating vs. those not eating fish in this study was consistent with the result of the majority. Study A35 compared results of EPA+DHA taken in impractically large amounts with similar large amounts of corn oil that in such amounts also could have been beneficial. Thus this was not a true direct valuation of the benefit of EPA+DHA.

Study A19 that was based on amounts of EPA and DHA in blood showed a substantial reduction in risk for higher values. Study A18 found a five fold reduction in risk of sudden coronary death associated with different amounts of EPA+DHA in blood. Clinical study A39 also found a 2/3rds reduction in risk of sudden death (but not for coronary disease per se) for differing amounts of EPA+DHA in blood. The meta analysis of 11 clinical studies found an average reduction in risk of 30% for fatal CHD and for sudden death for various differences in amounts of EPA+DHA. And this meta analysis found similar results for EPA+DHA taken in supplements vs. that taken in fish. Overall, it seems well-confirmed that EPA+DHA taken in the amounts of only a half to one gram per day usually will reduce risk of heart disease death about in half.

Some additional studies and risk ratios are referenced in a very extensive summary report on Omega-3 fatty acids research listed in the NIH Office of Dietary Supplements, http://odp.od.nih.gov/ods. Some studies therein not included below are not quantitatively useful, or have excessive error margins.

TABLE A

EFFECT of POLYUNSATURATED FATS on CORONARY HEART DISEASE

Study

Sex

Scope

Risk Ratio

Error Margin

Basis

Diff in Amount

Cause

Notes

TOTAL POLY UNSATURATED FATS

Ascherio, A, BMJ 1996, 313:84

Hlth Professionals Study, N=734

1.04

0.80

0.82-1.33

0.63-1.03

5ths

3.5-7.1%

0.4-0.7%

All CHD

Linoleic Acid

Linolenic Acid

(key poly-fats)

Hu, FB N Engl J Med,

1997, 337:1491

Nurses Study

N= 658

0.83

0.62

0.67-1.02

0.46-0.85

5ths

2.9-6.4%

for + 5% of Calories

All CHD

Multivariable adjust

Multivar + transfat

n-3 UNSATURATED FATTY ACIDS

OBSERVATION STUDIES

Dolecek,TA World Rev nutr diet 1991, 22:205

MRFIT Study of12,900 at high risk for coronary disease, 10 yrs

0.66

0.59

0.41-1.05

P=0.004

5ths linolenic

EPA+DHA

0.87-2.8 g/d

0-0.66 g/d

CVD death

Ascherio A,,Br Med J 1996,313:84

734 CHD for 43,750 Health Professionals

0.41

P < 0.01

5ths of Linolenic Acid

0.8-1.5 gms.day

All CHD

Age adjusted rr=1.05 (1.03 on fatal CHD but heavily confounded. Value 0.41 uncertain

A10

Ascherio,A, N Engl J Med 1995,332:977

Hlth Professional Study, 1543 events of 45,000

1.14

0.86-1.51

5ths

DHA+EPA

0.07-0.98 g/day

All CHD

Multivariable adjust. Unadjusted was similar

A11

Siscovick,TE, 1995 JAMA 274:1363

M&W

334 cases and controls. Univ of Washington

0.5

O.4-0.8

equiv 1 fatty fish/wk

1.5 g, EPA +DHA/wk via fish

CHD cardiac arrest

rr-0.3 (0.2-0.6) for quartiles of polyunsats in blood

A12

Albert, MA JAMA 1998; 279:23

133 Sudden coronary deaths of 20,500, Physicians Health Study

1.0

0.58

0.34

0.60

0.43

Base

0.28-1.21

0.15-0.75

0.29-1.27

0.20-0.93

5ths of

DHA+EPA

0.3 gm/mo

0.3-2.7 g/mo

2.7-4.9 g/mo

4.0-7.4 g/m

>7.4 g/mo

Sudden cardiac death

computed from fish consumption

A13

Hu, FB, Am J of Clin Nutr 1999, 69:890

232 events fatal MI, 597 of non-fatal MI on 76,000 Nurses, 10 yrs

1.00

0.99

0.90

0.67

0.55

0.85

Base

0.66-1.48

0.59-1.39

0.42-1.09

0.32-0.94

0.61-1.19

Alpha Linolenic Acid

0.71 gm/d

0.86

0.98

1.12

1.7

Fatal MI

Non-fatal MI

From foods as oil & vinegar, mayonnaise, margerines,

A14

Rissanen, T, Circulation, 2000, 102:2677

194 Events of 1871 men, coronary free

0.56

0.35-0.99

5fths of DHA+EPA

2.1-3.9% of fatty acids

All CHD

Men with avg hair amt of mercury. risk = 0.33 for men with low mercury

A15

Djousse, L, Am J Clin Nutr 2001, 74:612

M&W

362 events of 2024 men and 123 events of 2382 women. All CHD free, but 1/2 selected were at higher risk

0.60

0.54

0.53

1.0

0.66

0.70

0.49

0.66

Base

0.43-0.83

0.38-0.74

0.38-0.77

0.38-0.74

Base

0.36-1.19

0.39-1.28

0.27-0.89

0.40-1.10

Alpha Linolenic Acid

0.53

0.67

0.78

0.90

1.14

0.46

0.58

0.65

0.76

0.96

All CHD

Men

Women

A16

Oomen, CM, Am J Clin Nutr 2001, 74:457

98 CHD events of 667 elderly, Zutphen Elderly Study, 10 yrs

0.97

0.58-1.63

Alpha Linolenic

acid

0.4-0.65 est % of energy

All CHD

Diff in amt tested is very small and error margin high. Heavy

interaction With TransFats

A17

Hu, FB, JAMA 2002, 287:1815

1513 CHD events (484 deaths) of 85,000 Nurses

1.0

0.93

0.78

0.68

0.67

0.61

0.77

Base

0.78-1.09

0.65-0.93

0.56-0.82

0.55-0.81

0.46-0.82

0.58-1.02

5thsof DHA + EPA from fish

0.03%calorie

0.05

0.08

0.14

0.24

All CHD

Also rr was lower with larger amt of linoleic acid

no aspirin

with aspirin

A18

Albert, CM, N Engl J Med 2002, 346:1113

94 men from Physicians Health Study that suffered sudden death

1.0

0.55

0.28

0.19

Base

0.18-1.7

0.17-0.83

0.05-0.71

4ths of DHA+EPA

in blood

+ other

3.58%

4.76%

5.63%

6.87%

% in blood

Sudden CHD death

vs % of n-3 acids in blood

rr=0.10 in 4th quartile with further adjustments

A19

Singh RB, 2002, Lancet 360:1455

M&W

Case control, 499 experimental vs. 401 controls in India

0.51

0.38

P < 0.001

p < 0.015

diet intervention

Linolenic Acid

0.8 vs. 1.8 gm/day

All CHD

Sudden Dtth

A19

Erkkila AT, Am J Clin Nutr 2003, 78:65

M&W

285 men and 130 women with CHD over 5 yrs, Finland

0.44

0.33

0.31

0.82

.11-0.93

.12-0.93

.11-0.87

.31-2.16

linolenic

EPA

DHA

Linoleic

0.7-0.95%est

0.9-2.5%est

0.5-0.9%est

42-53%est

% in blood lipids

CVD death

same

High Error Margin

A20

Ingeborg, A, J. Nutr,2004 134:919

M&W

Meta Analysis of 5 studies

0.79

0.60-1.04

Linolenic Acid

avg diff in amts cited are uncertain

Fatal CHD

Selection of risks in two studies questionable. rr of 0.5-0.6 possible

CLINICAL STUDIES

A30

Burr, ML, Lancet 1989, 2(8666):757

2033 men having had MI, 2 yr all cause death

0.79

Those advised to eat 2-3 portions fatty fish/week

Poorly quantified, lesser effect of fat, fiber.

A31

Singh, RB, Cardiovasc Drugs Ther 1997; 11:485

M&W

122 fish oil (EPA) vs. Placebo, 1 yr

120 alpha-linolenic vs placebo, 1 yr

0.71

0.81

0.48-1.11

0.56-1.2

All had MI at start

1.08 gm/day

2.9 gm/day

both EPA & linolenic showed less arrhythmias,

A32

GISSI (Italy) Lancet 1999; 354:447

M&W

2836 CHD survivors vs. 2828 control, 3-5 years clinical study

0.70

0.56-0.87

quartiles

1 gm/day of n-3 poly fat supplement vs none

A34

Guallar, E, Arteriosclerosis, Thrombosis and Vascular Biology 1999, 19:1111

M&W

639 CHD patients and 700 controls

0.42

0.22-0.81

Alpha Linolenic

Acid

quintiles

of amounts in blood

further CHD

Adjusted risk of 0.68

may be in error

A35

Dennis, Wt, Am J Clin Nutr 2001, 74:50

M&W

300 Coronary patients assigned to high dose EPA+DHA vs 300 to Corn Oil

1.19

0.76-1.86

EPA+DHA

and Corn oil

4 gms/day of each

Fatal and non fatal recurrence

Corn oil also high in poly-unsats, thus result dubious

A36

Bucher, HC, Am J Med 2000, 112:298

M&W

Meta analysis of 11 randomized studies, n-3 acids vs. placebo

0.8

0.7

0.5-1.2

0.6-0.8

0.6-0.9

n-3 acids

various amounts in different studies

fatal CHD

sudden death

No difference in diet or supplements

A37

Marchioli, R;(GISSI), Circulation 2002, 105:1897

M&W

2836 CHD survivors vs. 2828 control, 3-5 years clinical study

0.67

0.65

0.46

0.56-0.86

0.51-0.82

n-3 fatty acids, presumed DHA+EPA

1 gm/day

CHD death

CVD death

sudden death

Risk showed little variation over 3-42 mo

A38

Guallar, E, N Engl J Med 2002, 347:1747

684 men with first MI in 8 Europe countries & 724 controls

0.8

0.59

2.16

0.53-1.23

0.30-1.19

1.09-4.29

5ths DHA

5ths mercury

0.1 to 0.44%

in tissue

0.11-0.65 ug/g from toenails

unadjusted

Adj mercury

mercury risk

Risks vs DHA before and after adj for mercury

A39

Lemaitre RN, Am J Clin Nutr 2003, 77:319

M&W

179 coronary free with 179 controls, measurements in blood 2 yrs before event for older persons age 65+

0.32

0.97

0.48

1.07

2.42

1.10

O.13-.78

0.71-1.33

0.24-0.96

0.81-1.41

1.07-5.43

0.83-1.46

EPA+DHA

same

Linolenic

same

Linoleic

same

2.93.7% bld

same

0.013-0.20

same

18.5-21.2

same

Fatal CHD

Nonfatal

Fatal CHD

NonfatalCHD

Fatal CHD

NonfatalCHD

FISH INTAKE

A50

Kromhout, D, N Engl J Med 1985;312:1205

Eskimos, Greenland 78 cases of 852

0.51

30+ g fish/ day vs. none

(=2.7+ fish per week)

CHD death

20 years followup

same w or w/o adjustments

A51

Ascherio,A, N Engl J Med 1995,332:977

Hlth Professionals Study, 1543 events of 45,000

1.14

0.74

0.86-1.51

0.44-1.23

6+ wk vs. 1- per month

Any fish vs no fish

All CHD

All Cases, adj

Use 10+ years

No evident dose relationship

A52

Morris, MC; 1995, Am J Epidem 142:166

281 events of 20,500 Physicians Health Study

1.0

1.6

1.4

1.2

1.1-2.3

1.0-2.0

0.6-2.2

<1 fish/wk

1 fish/wk

3 fish/wk

5+ fish/wk

See update va Albert, MA(1998)

A53

Kromhout, EJ, Int J of Epidem 1995, 24:340

M&W

58 events of 272, over 17 yrs in Netherlands elderly pop

0.51

0.29-0.89

60% Fish eaters vs 40% non fish eaters

All CHD

No effect on cancer or total mortality.

A54

Daviglus, ML, N Engl J Med 1997; 336:1046

430 CHD deaths from 1822 over 30 yrs, Chicago Western Electric Study

1.00

0.88

0.80

0.62

0.60-1.28

0.63-1.22

0.61-1.17

0.40-0.94

0 gm/day

1-17 gm/day

18-34 gm/d

35+ gm/d

All CHD

most benefit for non-sudden death

Definition of sudden death may be doubtful

A55

Albert, MA JAMA 1998; 279:23

133 Sudden coronary deaths of 20,500, Physicians Health Study

1.0

0.64

0.47

0.51

0.39

Base

0.26-1.58

0.23-0.98

0.25-1.04

0.15-0.96

< 1 /month

1-3 /month

1- <2/week

2- <5/week

5+ /week

Sudden Death No effect on rr of MI

adjusted values

Updates 1995 paper.

A56

Albert, MA, Same Study as above

306 CHD deaths of 20,500, Physicians Health Study

1.0

1.18

0.82

0.91

0.81

Base

0.59-2.36

0.45-1.51

0.50-1.66

0.49-1.33

< 1 /month

1-3 /month

1- <2/week

2- <5/week

5+ /week

All CHD death.

Updates of 1995 paper that found no effect

A57

Oomen, CM, 2000, Am J Epidem, 2000, 151:999

1,088 Finland; 1097 Italy; 553 Dutch in Seven Countries study

0.66

1.08

0.49-090

0.76-1.53

4ths

fatty fish

lean fish

CHD mortality

A58

Hu, FB, JAMA 2002, 187:1815

1513 CHD events (484 deaths) of 85,000 Nurses

1.00

0.79

0.71

0.69

0.66

0.75

0.59

Base

0.64-0.97

0.58-0.87

0.55-0.88

0.50-0.89

0.49-1.16

0.39-0.90

5ths

mw aspirin

w/o aspirin

nill

1-3/ month

1 per week

2-4 / week

5+ /week

5+/wk

All CHD

A59

Hu, FB, Circulation 2003, 107:1852

362 events of 5100 Diabetic Women in Nurses Study, CVD free at start

1.0

0.70

0.60

0.64

0.36

Base

0.48-1.03

0.42-0.85

0.42-0.99

0.20-0.66

overall fish con-

sumption

<1/month

1-3 per mo

1 per week

2-4 per wk

5+ per wk

All CHD

A60

Erkkila AT, Am J Clin Nutr 2003, 78:1

M&W

285 men and 130 women with CHD over 5 yrs, Finland

1.00

0.64

0.45

Base

0.28-1.47

0.19-1.09

0 gm/day

e 30 gm/day

e 85 gm/day

ALL CVD

includes stroke but small n's

A61

Mozaffarian D, Circulation 2003, 107:1372

M&W

610 events, 247 fatal of 3910 in US, avg age 72. Other fish is Tuna + broiled, baked; fried fish includes this plus fish sandwiches

0.47

0.32

0.67

1.37

1.54

1.93

0.27-0.82

0.15-0.70

0.42-1.07

0.48-3.90

0.82-2.58

0.91-4.08

Otherfish

same

FriedFish

same

nil to >3 wk

same

nil to >3 wk

nil to 2 wk

nil to >3 wk

All CHD dth

Arrhythm dth

Non-fatal

All CHD dth

Arrhythm dth

Non-fatal dth

Dose related

same

TABLE B

EFFECT of POLYUNSATURATED FATS on STROKE

n-3 UNSATURATED FATTY ACIDS and STROKE

Prospective & Case Control Studies

Study

Sex

Scope

Risk Ratio

Error Margin

Basis

Diff in Amount

Cause

Notes

Simon, JA, Stroke, 1995; 26:778, MRFIT study

96 high risk men with stoke vs 96 controls, 6.9 yrs

0.72

p<0.05

~linolenic

0.06% in blood

Fatal plus non-fatal stroke

Possible benefits of EPA and DHA

Iso, H, JAMA, 2001. 285:304

574 events , 303 ischemic of 80,000 Nurses over 14 years

0.72

0.53-0.99

DHA+EPA from diet

0.23 - 0.24% of energy

All strokes

FISH CONSUMPTION and STROKE

Prospective & Case Control Studies

B10

Keli, SO, Stroke, 1994: 25:328

552 men 50-69 yrs in Zutphen Netherlands, over 15 yrs

0.49

0.24-0.99

<20 gm/day vs >20gm/day

All stroke

Avg consumption very high at 17.9 gm/day

B11

Orencia, Stroke; 1996 27:204

76 events of 1847 men in Chicago, IL area. 30 yr risk

1.00

0.94

0.89

1.28

0.43-2.33

0.58-1.51

0.56-1.43

0.76-2.14

No Fish

1-17gm/day

18-34 gm/d

35+ gm/d

Fatal and Non Fatal Stroke

Adj values similar

B12

Gillium RF, Arch Int Med, 1996 156:537

M&W

Sample of M&W from NHANES Study, 12 yrs followup

0.55

0.32-0.93

Fish cons

Never vs 1+/wk

fatal and non-fatal

B13

Iso, H, JAMA, 2001. 285:304

574 events , 303 ischemic of 80,000 Nurses

1.0

0.93

0.78

0.73

0.48

Base

0.65-1.34

0.55-1.12

0.47-1.14

0.21-1.06

p for trend = 0.06

< 1/ month

1-3 times/mo

1 per week

2-4 per week

5+ per week

Risk of all Stroke

TABLE C

EFFECT of POLYUNSATURATED FATS on DEATH from ALL CAUSES

Study

Sex

Scope

Risk Ratio

Error Margin

Basis

Diff in Amount

Cause

Notes

n-3 UNSATURATED FATTY ACIDS and ALL-CAUSE DEATH

Prospective & Case Control Studies

Albert, MA JAMA 1998; 279:23

1652 all cause deaths of 20,500, Physicians Health Study

1.0

0.79

0.71

0.70

0.73

Base

.59-1.0

.55-.91

.54-.89

.55-.96

Fish con-

sumption

< 1 /month

1-3 /month

1- <2/week

2- <5/week

5+ /week

Total Mortality

Updates 1995 paper on this study.

p = .045

Clinical Studies

C10

Burr, ML Lancet 1989, 2(8666):757

2003 who had recovered from MI over 2 years

0.71

0.5-0.9

Fish cons-

umption

2-3 portions per wk in fish intake

Total Mortality

No effect on incidence of re-infarction.

C11

GISSI (Italy) Lancet 1999; 354:447

M&W

2836 CHD survivors vs. 2828 control, 305 year clinical study

0.80

0.67-0.96

quartiles

1 gm/day of n-3 poly fat supplement vs none

C12

Bucher, HC, Am J Med 2000, 112:298

M&W

Meta analysis of 11 randomized studies, n-3 acids vs. placebo

0.80

0.7-0.9

High vs. Low amounts

No difference in diet or supplements

t values of the coefficient based on EPA+DHA and from fish vary from 4 to 8+ vs 2 needed for 95% significance.

Risk ratio=Exp(-0.0670 * sqr(grams/day of fish)). For all fish, researched probably 0.4-0.5 gm EPA+DHA per 100 grams of fish. From 37 researched comparisons of non-fried fish, r=0.90; t of coefficient 12.2

Risk ratio= exp(0.648 - 0.83 * gms/day of linolenic acid) r=0.87; t of coefficient=6.1

(4) Risk of cardiovascular death from all other Polyunsaturated fats: (Assumes average population is 8.5% of calories)

Fish Consumption and EPA+DHA in the US
Fish Type	Consumption, grams/day/ capita	% of total Consumption	% of EPA + DHA
Tuna	2.63	20.4	0.26
Shrimp	1.63	12.7	0.35
Cod	1.12	8.8	0.19
Salmon	1.02	8.0	1.45
Flounder	0.46	3.6	0.20
Catfish	0.34	2.7	0.18
Haddock	0.25	1.9	0.24
Herring	0.09	0.07	1.5
Mackeral	0.09	0.07	2.0
All Fish	12.83	100	0.50 est