Seafood/plant-based omega-3 fatty acids lower heart disease incidence

Results  The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male.

In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA.

Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not.

Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses.

Conclusions and Relevance  On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.


Eating seafood and Dementia/Alzheimer’s

 APOE ε4 (Alzheimer’s gene) and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

In the article “APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline,” van de Rest and colleagues examined the connection between the amount of seafood eaten per week and cognitive decline over approximately 5 years in older adults living in retirement communities. The researchers were also interested in learning more about how a gene called APOE ε4 might influence the effect that seafood consumption has on cognitive decline.1 The community-based study was designed to better understand changes in thinking and motor abilities and the risk of Alzheimer disease (AD) in older adults. The study was called the Rush Memory and Aging Project or MAP.2

Alzheimer’s Diease is the most common type of dementia

In 2015, 46.8 million people worldwide had dementia, and this number is expected to double every 20 years. AD is the most common type of dementia.3 There is currently no proven therapy that can prevent or cure AD, so it is important to understand and identify factors that might prevent or delay the onset of AD and other dementias. Researchers are interested in the fats contained in fish and seafood. These fats are called omega-3 fatty acids. These fats are of interest to researchers because the brain contains a high amount of omega-3 fatty acids. It is also known that these fatty acids are needed for a healthy brain. With aging, these fatty acids may decrease, so keeping healthy levels of them in the brain may prevent or delay cognitive decline. The APOE ε4 gene is involved in moving cholesterol to cells, including brain cells. This gene may also have an effect on how omega-3 fatty acids are moved into brain cells. People who have the APOE ε4 gene have an increased risk of AD. Those over age 65 are at the highest risk for AD.


The participants were older adults without dementia in the MAP study whose information was collected every year for about 4.9 years. The average age of this group was 81.4 years and about 75% were women. The MAP study followed the same group of people who lived in retirement communities in the Chicago area from 2004 to 2013. Every year, they filled out a survey about their diet. Researchers also gave them tests to rate their thinking ability. The diet survey asked about eating things like tuna fish sandwiches, fish sticks or fish cakes, fresh fish, and shellfish like shrimp, crab, or lobster. Complete information from 915 participants on diet, thinking ability, and the APOE ε4 gene was used to produce the study results.


This study showed that older adults without dementia who eat one or more servings of seafood per week have less cognitive decline than those who eat less than one serving of seafood per week. The study showed that seafood consumption was related to 2 specific areas of brain function. One of these areas was the ability to remember facts, like knowing the names of different types of animals. This is important for clear communication. The other area was the ability to learn and process new information. This is important in difficult decision-making during tasks like driving. The researchers did not see an effect on overall cognitive function. A smaller group of participants reported taking fish oil supplements (17.5% of the total participants). They had less decline in overall cognitive function and “episodic memory” than those who did not supplement with fish oil. Episodic memory involves the ability to remember specific events, like where you parked your car or your wedding day. The researchers saw a similar and bigger effect in those participants that had the APOE ε4 gene (19.5% of the total participants). Because this APOE ε4 effect has not been seen in other studies, the researchers noted that more studies need to be done to better understand how this gene influences the protective effect of eating seafood.

Written by

Lynne Shinto, ND, MPH


Neurology May 31, 2016   vol. 86  no. 22  e231-e233

Healthy Oils

Healthy Oils

You need to have a healthy liver to balance any essential oil metabolism, absorption and conversion into the body’s required energy.

This is recorded by Connie from Hemp oil contains 2% of stearodonic acid –omega 3

The info below is from

Essential Fatty Acids

• Alpha-linolenic acid (ALA), an omega-3 fatty acid, and linoleic acid (LA), an omega-6 fatty acid, are considered essential fatty acids because they cannot be synthesized by humans. (More Information)
• The long-chain omega-6 fatty acid, arachidonic acid (AA), can be synthesized from LA. (More Information)
• The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can be synthesized from ALA, but EPA and DHA synthesis may be insufficient under certain conditions. (More Information)
• Typical Western diets tend to be much higher in omega-6 fatty acids than omega-3 fatty acids. (More Information)
• While DHA appears to be important for visual and neurological development, it is not yet clear whether feeding infants formula enriched with DHA and AA enhances visual acuity or neurological development in preterm or term infants. (More Information)
• A large body of scientific research suggests that higher dietary omega-3 fatty acid intakes are associated with reductions in cardiovascular disease risk. Thus, the American Heart Association recommends that all adults eat fish, particularly oily fish, at least twice weekly. (More Information)
• The results of randomized controlled trials indicate that increasing omega-3 fatty acid intake can decrease the risk of myocardial infarction (heart attack) and sudden cardiac death in individuals with coronary heart disease (CHD). (More Information)
• Low DHA status may be a risk factor for Alzheimer’s disease and other types of dementia, but it is not yet known whether DHA supplementation can help prevent or treat such cognitive disorders. (More information)
• Increasing EPA and DHA intake may be beneficial in individuals with type 2 diabetes, especially those with elevated serum triglycerides. (More Information)
• Randomized controlled trials have found that fish oil supplementation decreases joint tenderness and reduces the requirement for anti-inflammatory medication in patients with rheumatoid arthritis. (More Information)
• Although limited preliminary data suggest that omega-3 fatty acid supplementation may be beneficial in the therapy of depression, bipolar disorder, and schizophrenia, larger controlled clinical trials are needed to determine therapeutic efficacy. (More Information)

Introduction: polyunsaturated fatty acids

Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFA), meaning they contain more than one cis double bond (1). In all omega-3 fatty acids, the first double bond is located between the third and fourth carbon atom counting from the methyl end of the fatty acid (n-3). Similarly, the first double bond in all omega-6 fatty acids is located between the sixth and seventh carbon atom from the methyl end of the fatty acid (n-6). Scientific abbreviations for fatty acids tell the reader something about their chemical structure. One scientific abbreviation for alpha-linolenic acid (ALA) is 18:3n-3. The first part (18:3) tells the reader that ALA is an 18-carbon fatty acid with three double bonds, while the second part (n-3) tells the reader that the first double bond is in the n-3 position, which defines it as an omega-3 fatty acid.
Although humans and other mammals can synthesize saturated fatty acids and some monounsaturated fatty acids from carbon groups in carbohydrates and proteins, they lack the enzymes necessary to insert a cis double bond at the n-6 or the n-3 position of a fatty acid (1). Consequently, omega-6 and omega-3 fatty acids are essential nutrients. The parent fatty acid of the omega-6 series is linoleic acid (LA; 18:2n-6), and the parent fatty acid of the omega-3 series is ALA (Figure 1). Humans can synthesize long-chain (20 carbons or more) omega-6 fatty acids, such as dihomo-gamma-linolenic acid (DGLA; 20:3n-6) and arachidonic acid (AA; 20:4n-6) from LA and long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) from ALA (see Metabolism and Bioavailability below). It has been estimated that the ratio of omega-6 to omega-3 fatty acids in the diet of early humans was 1:1 (2), but the ratio in the typical Western diet is now almost 10:1 due to increased use of vegetable oils rich in LA as well as reduced fish consumption (3). A large body of scientific research suggests that increasing the relative abundance of dietary omega-3 fatty acids may have a number of health benefits.

Metabolism and Bioavailability

Prior to absorption in the small intestine, fatty acids must be hydrolyzed from dietary fats (triglycerides, phospholipids, and cholesterol) by pancreatic enzymes (4). Bile salts must also be present in the small intestine to allow for the incorporation of fatty acids and other fat digestion products into mixed micelles. Fat absorption from mixed micelles occurs throughout the small intestine and is 85-95% efficient under normal conditions. Humans can synthesize longer omega-6 and omega-3 fatty acids from the essential fatty acids LA and ALA, respectively, through a series of desaturation (addition of a double bond) and elongation (addition of two carbon atoms) reactions (Figure 2) (5). LA and ALA compete for the same elongase and desaturase enzymes in the synthesis of longer polyunsaturated fatty acids, such as AA and EPA. Although ALA is the preferred substrate of the delta-6 desaturase enzyme, the excess of dietary LA compared to ALA results in greater net formation of AA (20:4n-6) than EPA (20:5n-3) (6). The capacity for conversion of ALA to DHA is higher in women than men. Studies of ALA metabolism in healthy young men indicate that approximately 8% of dietary ALA is converted to EPA and 0-4% is converted to DHA (7). In healthy young women, approximately 21% of dietary ALA is converted to EPA and 9% is converted to DHA (8). The better conversion efficiency of young women compared to men appears to be related to the effects of estrogen (6, 9). Although ALA is considered the essential omega-3 fatty acid because it cannot be synthesized by humans, evidence that human conversion of EPA and, particularly, DHA is relatively inefficient suggests that EPA and DHA may also be essential under some conditions (10, 11).

Biological Activities: Membrane Structure and Function

Omega-6 and omega-3 PUFA are important structural components of cell membranes. When incorporated into phospholipids, they affect cell membrane properties such as fluidity, flexibility, permeability and the activity of membrane bound enzymes (12). DHA is selectively incorporated into retinal cell membranes and postsynaptic neuronal cell membranes, suggesting it plays important roles in vision and nervous system function.
DHA is found at very high concentrations in the cell membranes of the retina; the retina conserves and recycles DHA even when omega-3 fatty acid intake is low (13). Animal studies indicate that DHA is required for the normal development and function of the retina. Moreover, these studies suggest that there is a critical period during retinal development when inadequate DHA will result in permanent abnormalities in retinal function. Recent research indicates that DHA plays an important role in the regeneration of the visual pigment rhodopsin, which plays a critical role in the visual transduction system that converts light hitting the retina to visual images in the brain (14).
Nervous System
The phospholipids of the brain’s gray matter contain high proportions of DHA and AA, suggesting they are important to central nervous system function (15). Brain DHA content may be particularly important, since animal studies have shown that depletion of DHA in the brain can result in learning deficits. It is not clear how DHA affects brain function, but changes in DHA content of neuronal cell membranes could alter the function of ion channels or membrane-associated receptors, as well as the availability of neurotransmitters (16).

Eicosanoid Synthesis

Eicosanoids, derived from 20-carbon PUFA, are potent chemical messengers that play critical roles in immune and inflammatory responses. During an inflammatory response, DGLA, AA, and EPA in cell membranes can be metabolized by enzymes known as cyclooxygenases and lipoxygenases to form prostaglandins and leukotrienes, respectively (Figure 2). In those who consume typical Western diets, the amount of AA in cell membranes is much greater than the amount of EPA, resulting in the formation of more eicosanoids derived from AA than EPA. However, increasing omega-3 fatty acid intake increases the EPA content of cell membranes, resulting in higher proportions of eicosanoids derived from EPA. Physiological responses to AA-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and coagulation than eicosanoids derived from AA (3, 17).

Regulation of Gene Expression

The results of cell culture and animal studies indicate that omega-6 and omega-3 fatty acids can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation (17, 18). Although the mechanisms require further clarification, omega-6 and omega-3 fatty acids may regulate gene expression by interacting with specific transcription factors, including peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs) (19). Multiple mechanisms are involved in these regulatory schemes (20). In many cases, PUFA act like hydrophobic hormones (e.g., steroid hormones) to control gene expression. In this case, PUFA bind directly to receptors like PPARs. These receptors bind to the promoters of genes and function to increase/decrease transcription of genes. In other cases, PUFA regulate the abundance of transcription factors inside the cell’s nucleus (20). For these factors, the mechanism for PUFA control is less clear. Two examples include NFκB and SREBP-1. NFκB is a transcription factor involved in regulating the expression of multiple genes involved in inflammation. Omega-3 PUFA suppress NFκB nuclear content thus inhibiting the production of inflammatory eicosanoids and cytokines. SREBP-1, is a major transcription factor controlling fatty acid synthesis, both de novo lipogenesis and PUFA synthesis (21). Dietary PUFA can suppress SREBP-1, which decreases the expression of enzymes involved in fatty acid synthesis and PUFA synthesis (22, 23). In this way, dietary PUFA function as feedback inhibitors of all fatty acid synthesis.

Deficiency: Essential Fatty Acid Deficiency

Clinical signs of essential fatty acid deficiency include a dry scaly rash, decreased growth in infants and children, increased susceptibility to infection, and poor wound healing (24). Omega-3, omega-6, and omega-9 fatty acids compete for the same desaturase enzymes. The desaturase enzymes show preference for the different series of fatty acids in the following order: omega-3 > omega-6 > omega-9. Consequently, synthesis of the omega-9 fatty acid eicosatrienoic acid (20:3n-9, mead acid, or 5,8,11-eicosatrienoic acid) increases only when dietary intakes of omega-3 and omega-6 fatty acids are very low; therefore, mead acid is one marker of essential fatty acid deficiency (25). A plasma eicosatrienoic acid:arachidonic acid (triene:tetraene) ratio greater than 0.2 is generally considered indicative of essential fatty acid deficiency (24, 26). In patients who were given total parenteral nutrition containing fat-free glucose-amino acid mixtures, biochemical signs of essential fatty acid deficiency developed in as little as 7-10 days (27). In these cases, the continuous glucose infusion resulted in high circulating insulin levels, which inhibited the release of essential fatty acids stored in adipose tissue. When glucose-free amino acid solutions were used, parenteral nutrition up to 14 days did not result in biochemical signs of essential fatty acid deficiency. Essential fatty acid deficiency has also been found to occur in patients with chronic fat malabsorption (28) and in patients with cystic fibrosis (29). Recently, it has been proposed that essential fatty acid deficiency may play a role in the pathology of protein-energy malnutrition (25).
Omega-3 Fatty Acid Deficiency
At least one case of isolated omega-3 fatty acid deficiency has been reported. A young girl who received intravenous lipid emulsions with very little ALA developed visual problems and sensory neuropathy; these conditions were resolved when she was administered an emulsion containing more ALA (30). Plasma DHA concentrations decrease when omega-3 fatty acid intake is insufficient, but no cutoff values have been established. Isolated omega-3 fatty acid deficiency does not result in increased plasma triene:tetraene ratios (1). Studies in rodents, however, have revealed significant impairment of n-3 PUFA deficiency on learning and memory (31, 32). These studies have prompted clinical trials in humans to assess the impact of omega-3 PUFA on cognitive development and cognitive decline (see:

Disease Prevention: Visual and Neurological Development

Because the last trimester of pregnancy is a critical period for the accumulation of DHA in the brain and retina, preterm infants are thought to be particularly vulnerable to adverse effects of insufficient DHA on visual and neurological development (33). Human milk contains DHA in addition to ALA and EPA, but until recently, ALA was the only omega-3 fatty acid present in conventional infant formulas. Although preterm infants can synthesize DHA from ALA, they generally cannot synthesize enough to prevent declines in plasma and cellular DHA concentrations without additional dietary intake. Therefore, it was proposed that preterm infant formulas be supplemented with enough DHA to bring plasma and cellular DHA levels of formula-fed infants up to those of breast-fed infants (34). Although formulas enriched with DHA raise plasma and red blood cell DHA concentrations in preterm and term infants, the results of randomized controlled trials examining measures of visual acuity and neurological development in infants fed formulas with or without added DHA have been mixed (35-38). Although several controlled trials found that healthy preterm infants fed formulas with DHA added showed subtle but significant improvements in visual acuity at two and four months of age compared to those fed DHA-free formulas (39), most randomized controlled trials found no differences in visual acuity between healthy preterm infants fed formulas with or without DHA added (36). Similarly, two randomized controlled trials that assessed general measures of infant development at 12 and 24 months of age found no difference between preterm infants fed formula with or without DHA added (40, 41). However, two recent randomized controlled trials assessing infant development at 18 months of age reported beneficial effects of DHA supplementation in preterm infants, but one of these trials found a significant effect only in boys (42, 43). Infant formulas enriched with DHA are also commercially available for term infants, but the results of randomized controlled trials of these formulas on visual acuity and development in term infants have also been mixed (37, 44-47; reviewed in 38 and 48). While DHA appears to be important for visual and neurological development, it is not yet clear whether feeding infants formula enriched with DHA enhances visual acuity or neurological development in preterm or term infants (49).

Pregnancy and Lactation

Although infant requirements for DHA have been the subject of a great deal of research, there has been relatively little investigation of maternal requirements for omega-3 fatty acids, despite the fact that the mother is the sole source of omega-3 fatty acids for the fetus and exclusively breast-fed infant (50). The results of randomized controlled trials during pregnancy suggest that omega-3 fatty acid supplementation does not decrease the incidence of gestational diabetes, pregnancy-induced hypertension or preeclampsia (51-53), but may result in modest increases in length of gestation, especially in women with low omega-3 fatty acid consumption. In healthy Danish women, fish oil supplementation that provided 2.7 g/day of EPA + DHA increased the length of gestation by an average of four days (52). More recently, consumption of only 0.13 g/day of DHA from enriched eggs during the last trimester of pregnancy increased the length of gestation by an average of six days in a low-income population in the United States (53). A recent meta-analysis of six randomized controlled trials in women with low-risk pregnancies found that omega-3 PUFA supplementation during pregnancy resulted in an increased length of pregnancy by 1.6 days (54). In European women with high-risk pregnancies, fish oil supplementation, which provided 2.7 g/day of EPA + DHA during the last trimester of pregnancy, lowered the risk of premature delivery from 33% to 21% (55). However, a meta-analysis of randomized controlled trials in women with high-risk pregnancies found that supplementation with long-chain PUFA did not affect pregnancy duration or the incidence of premature births but decreased the incidence of early premature births ( 200 mg/dl) to be an independent risk factor for cardiovascular disease (118). Numerous controlled clinical trials in humans have demonstrated that increasing intakes of EPA and DHA significantly lower serum triglyceride concentrations (119). The triglyceride-lowering effects of EPA and DHA increase with dose (120), but clinically meaningful reductions in serum triglyceride concentrations have been demonstrated at doses of 2 g/day of EPA + DHA (3). In its recommendations regarding omega-3 fatty acids and cardiovascular disease (see Intake Recommendations below), the American Heart Association indicates that an EPA + DHA supplement may be useful in patients with hypertriglyceridemia (87).
Summary: Omega-3 and Omega-6 PUFA and Cardiovascular Disease Prevention
The results of epidemiological studies and randomized controlled trials suggest that replacing dietary SFA with omega-6 and omega-3 PUFA lowers LDL cholesterol and decreases cardiovascular disease risk. Additionally, the results of epidemiological studies provide strong evidence that increasing dietary omega-3 fatty intake is associated with significant reductions in cardiovascular disease risk through mechanisms other than lowering LDL cholesterol. In particular, increasing EPA and DHA intake from seafood has been associated with significant reductions in sudden cardiac death, suggesting that long-chain omega-3 fatty acids have anti-arrhythmic effects at intake levels equivalent to the amount in two small servings of oily fish per week. This amount of fish would provide about 400-500 mg/day of EPA + DHA (121). Thus, some researchers have proposed that the U.S. Institute of Medicine should establish a dietary reference intake (DRI) for EPA + DHA (122).

Alzheimer’s Disease and Dementia

Alzheimer’s disease is the most common cause of dementia in older adults. Alzheimer’s disease is characterized by the formation of amyloid plaque in the brain and nerve cell degeneration. Disease symptoms, including memory loss and confusion, worsen over time (123). Some epidemiological studies have associated high intake of fish with decreased risk of impaired cognitive function (124), dementia (125), and Alzheimer’s disease (125, 126). DHA, the major omega-3 fatty acid in the brain, appears to be protective against Alzheimer’s disease (127). Observational studies have found that lower DHA status is associated with increased risk of Alzheimer’s disease (128-130) as well as other types of dementia (129). In a cohort of the Framingham Heart Study, men and women in the highest quartile of plasma phosphatidylcholine DHA content had a 47% decreased risk of developing all-cause dementia and a 39% decreased risk of developing Alzheimer’s disease when compared to those in the lower three quartiles (131). Individuals in the top quartile consumed an average of three servings of fish weekly (0.18 g/day of DHA) (131). Thus, low DHA status may be a risk factor for Alzheimer’s disease, other types of dementia, and with cognitive impairment associated with aging.

Disease Treatment: Coronary Heart Disease
Dietary Intervention Trials

Total mortality and fatal MI decreased by 29% in male MI survivors advised to increase their weekly intake of oily fish to 200-400 g (7-14 oz)—an amount estimated to provide an additional 500-800 mg/day of long-chain omega-3 fatty acids (EPA + DHA) (132). In another dietary intervention trial, patients who survived a first MI were randomly assigned to usual care or advised to adopt a Mediterranean diet that was higher in omega-3 fatty acids (especially ALA) and lower in omega-6 fatty acids than the standard Western-style diet. After almost four years, those on the Mediterranean diet had a risk of cardiac death and nonfatal MI that was 38% lower than the group that was assigned to usual care (133). Although higher plasma ALA levels were associated with better outcomes, the benefit of the Mediterranean diet cannot be attributed entirely to increased ALA intakes since intakes of monounsaturated fatty acids and fruits and vegetables also increased. A recent intervention trial compared survival in MI survivors who followed a Mediterranean-style diet or a low-fat diet for an average of 46 months; total mortality and cardiovascular-related mortality did not differ between the two groups (134).

Diet rich in saturated fats is associated with worse global cognitive and verbal memory

A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders.  The results showed that diet rich in saturated fats (SFA) is associated with worse global cognitive and verbal memory trajectories, whereas higher Monounsaturated fats (MUFA) intake was related to better trajectories. ANN NEUROL 2012. May 17, 2012


Monounsaturated fats, or omega-9 fatty acids, are heart healthy. Dietary Guidelines for Americans recommends that you keep your total fat intake between 20 to 35 percent of daily calories, with the majority of fats consumed coming from sources of polyunsaturated and monounsaturated fatty acids. Foods rich in monounsaturated fats include nuts, oils, fish and other plant foods.

Vegetable Oils and Nuts

Many vegetable oils are rich in monounsaturated fats (also known as oleic acid). Those that offer the highest monounsaturated fatty acid content include high-oleic sunflower or safflower oil, as well as hazelnut, olive, canola, avocado, almond, peanut, corn, sesame, rice bran, soybean and cod liver oils. Soft tub margarine-like spreads made mostly from olive or canola oils are also rich in monounsaturated fats. Hazelnuts (or filberts), macadamia nuts, pecans, almonds, pistachios and cashews are rich food sources of monounsaturated fats. Thus, cashew and almond butter are also rich in this heart-healthy fat.


Among 6,183 older participants in the Women’s Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.

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