Fat/ja: Difference between revisions

Concerns about ''trans'' fatty acids in human diet were raised when they were found to be an unintentional byproduct of the [[fat hydrogenation|partial hydrogenation]] of vegetable and fish oils. While these ''trans'' fatty acids (popularly called "trans fats") are edible, they have been implicated in many health problems.

[[File:Triglyceride Hydrogenation&Isomerization V.1.png | thumb|330px | right | Conversion of ''cis'' to ''trans'' fatty acids in partial hydrogenation]]

The hydrogenation process, invented and patented by [[Wilhelm Normann]] in 1902, made it possible to turn relatively cheap liquid fats such as [[whale oil|whale]] or [[fish oil]] into more solid fats and to extend their shelf-life by preventing rancidification. (The source fat and the process were initially kept secret to avoid consumer distaste.) This process was widely adopted by the food industry in the early 1900s; first for the production of [[margarine]], a replacement for butter and shortening, and eventually for various other fats used in snack food, packaged baked goods, and deep fried products.

Full hydrogenation of a fat or oil produces a fully saturated fat. However, hydrogenation generally was interrupted before completion, to yield a fat product with specific melting point, hardness, and other properties. Partial hydrogenation turns some of the ''cis'' double bonds into ''trans'' bonds by an [[isomerization reaction]]. The trans configuration is favored because it is the lower energy form.

This side reaction accounts for most of the ''trans'' fatty acids consumed today, by far. An analysis of some industrialized foods in 2006 found up to 30% "trans fats" in artificial shortening, 10% in breads and cake products, 8% in cookies and crackers, 4% in salty snacks, 7% in cake frostings and sweets, and 26% in margarine and other processed spreads. Another 2010 analysis however found only 0.2% of trans fats in margarine and other processed spreads. Up to 45% of the total fat in those foods containing man-made ''trans'' fats formed by partially hydrogenating plant fats may be ''trans'' fat. Baking shortenings, unless reformulated, contain around 30% ''trans'' fats compared to their total fats. High-fat dairy products such as butter contain about 4%. Margarines not reformulated to reduce ''trans'' fats may contain up to 15% ''trans'' fat by weight, but some reformulated ones are less than 1% trans fat.

High levels of TFAs have been recorded in popular "fast food" meals. An analysis of samples of [[McDonald's]] French fries collected in 2004 and 2005 found that fries served in New York City contained twice as much trans fat as in [[Hungary]], and 28 times as much as in [[Denmark]], where trans fats are restricted. For [[Kentucky Fried Chicken]] products, the pattern was reversed: the Hungarian product containing twice the trans fat of the New York product. Even within the United States, there was variation, with fries in New York containing 30% more trans fat than those from [[Atlanta]].

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====Cardiovascular disease====

Numerous studies have found that consumption of TFAs increases risk of cardiovascular disease. The [[Harvard School of Public Health]] advises that replacing TFAs and saturated fats with ''cis'' monounsaturated and polyunsaturated fats is beneficial for health.

Consuming trans fats has been shown to increase the risk of [[coronary artery disease]] in part by raising levels of low-density lipoprotein (LDL, often termed "bad cholesterol"), lowering levels of high-density lipoprotein (HDL, often termed "good cholesterol"), increasing triglycerides in the bloodstream and promoting systemic inflammation.

The primary health risk identified for trans fat consumption is an elevated risk of [[coronary artery disease]] (CAD). A 1994 study estimated that over 30,000 cardiac deaths per year in the United States are attributable to the consumption of trans fats. By 2006 upper estimates of 100,000 deaths were suggested. A comprehensive review of studies of trans fats published in 2006 in the [[New England Journal of Medicine]] reports a strong and reliable connection between trans fat consumption and CAD, concluding that "On a per-calorie basis, trans fats appear to increase the risk of CAD more than any other macronutrient, conferring a substantially increased risk at low levels of consumption (1 to 3% of total energy intake)".

The major evidence for the effect of trans fat on CAD comes from the [[Nurses' Health Study]] – a [[cohort study]] that has been following 120,000 female nurses since its inception in 1976. In this study, Hu and colleagues analyzed data from 900 coronary events from the study's [[statistical population|population]] during 14 years of followup. He determined that a nurse's CAD risk roughly doubled ([[relative risk]] of 1.93, [[confidence interval|CI]]: 1.43 to 2.61) for each 2% increase in trans fat calories consumed (instead of carbohydrate calories). By contrast, for each 5% increase in saturated fat calories (instead of carbohydrate calories) there was a 17% increase in risk ([[relative risk]] of 1.17, [[confidence interval|CI]]: 0.97 to 1.41). "The replacement of saturated fat or trans unsaturated fat by cis (unhydrogenated) unsaturated fats was associated with larger reductions in risk than an isocaloric replacement by carbohydrates." Hu also reports on the benefits of reducing trans fat consumption. Replacing 2% of [[food energy]] from trans fat with non-trans [[unsaturated fat]]s more than halves the risk of CAD (53%). By comparison, replacing a larger 5% of food energy from saturated fat with non-trans unsaturated fats reduces the risk of CAD by 43%.

Another study considered deaths due to CAD, with consumption of trans fats being linked to an increase in mortality, and consumption of [[polyunsaturated fat]]s being linked to a decrease in mortality.

Trans fat has been found to act like saturated in raising the blood level of LDL ("bad cholesterol"); but, unlike saturated fat, it also decreases levels of HDL ("good cholesterol"). The net increase in LDL/HDL ratio with trans fat, a widely accepted indicator of risk for coronary artery disease, is approximately double that due to saturated fat. One randomized [[crossover study]] published in 2003 comparing the effect [[postprandial|of eating a meal]] on blood lipids of (relatively) cis and trans-fat-rich meals showed that [[cholesteryl ester]] transfer (CET) was 28% higher after the trans meal than after the cis meal and that lipoprotein concentrations were enriched in [[apolipoprotein]](a) after the trans meals.

The [[cytokine|citokyne test]] is a potentially more reliable indicator of CAD risk, although is still being studied. A study of over 700 nurses showed that those in the highest [[quartile]] of trans fat consumption had blood levels of [[C-reactive protein]] (CRP) that were 73% higher than those in the lowest quartile.

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====Breast feeding====

It has been established that ''trans'' fats in human [[breast milk]] fluctuate with maternal consumption of trans fat, and that the amount of trans fats in the bloodstream of breastfed infants fluctuates with the amounts found in their milk. In 1999, reported percentages of trans fats (compared to total fats) in human milk ranged from 1% in Spain, 2% in France, 4% in Germany, and 7% in Canada and the United States.

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====Other health risks====

* [[Alzheimer's disease]]: A study published in [[Archives of Neurology]] in February 2003 suggested that the intake of both trans fats and saturated fats promotes the development of Alzheimer disease, although not confirmed in an animal model. It has been found that trans fats impaired memory and learning in middle-age rats. The brains of rats that ate trans-fats had fewer proteins critical to healthy neurological function. Inflammation in and around the hippocampus, the part of the brain responsible for learning and memory. These are the exact types of changes normally seen at the onset of Alzheimer's, but seen after six weeks, even though the rats were still young.

* [[Cancer]]: There is no scientific consensus that consuming trans fats significantly increases cancer risks across the board. The American Cancer Society states that a relationship between trans fats and cancer "has not been determined." One study has found a positive connection between trans fat and prostate cancer. However, a larger study found a correlation between trans fats and a significant decrease in high-grade prostate cancer. An increased intake of trans fatty acids may raise the risk of breast cancer by 75%, suggest the results from the French part of the European Prospective Investigation into Cancer and Nutrition.

* [[Diabetes]]: There is a growing concern that the risk of [[diabetes mellitus type 2|type 2 diabetes]] increases with trans fat consumption. However, consensus has not been reached. For example, one study found that risk is higher for those in the highest [[quartile]] of trans fat consumption. Another study has found no diabetes risk once other factors such as total fat intake and BMI were accounted for.

* [[Obesity]]: Research indicates that trans fat may increase weight gain and abdominal fat, despite a similar caloric intake. A 6-year experiment revealed that monkeys fed a trans fat diet gained 7.2% of their body weight, as compared to 1.8% for monkeys on a mono-unsaturated fat diet. Although obesity is frequently linked to trans fat in the popular media, this is generally in the context of eating too many calories; there is not a strong scientific consensus connecting trans fat and obesity, although the 6-year experiment did find such a link, concluding that "under controlled feeding conditions, long-term TFA consumption was an independent factor in weight gain. TFAs enhanced intra-abdominal deposition of fat, even in the absence of caloric excess, and were associated with insulin resistance, with evidence that there is impaired post-insulin receptor binding signal transduction."

* [[Female infertility|Infertility in women]]: One 2007 study found, "Each 2% increase in the intake of energy from trans unsaturated fats, as opposed to that from carbohydrates, was associated with a 73% greater risk of ovulatory infertility...".

* [[Major depressive disorder]]: Spanish researchers analysed the diets of 12,059 people over six years and found that those who ate the most trans fats had a 48 per cent higher risk of depression than those who did not eat trans fats. One mechanism may be trans-fats' substitution for [[docosahexaenoic acid]] (DHA) levels in the [[orbitofrontal cortex]] (OFC). Very high intake of trans-fatty acids (43% of total fat) in mice from 2 to 16 months of age was associated with lowered DHA levels in the brain (p=0.001). When the brains of 15 major depressive subjects who had committed suicide were examined post-mortem and compared against 27 age-matched controls, the suicidal brains were found to have 16% less (male average) to 32% less (female average) DHA in the OFC. The OFC controls [[Reward (psychology)|reward]], reward expectation, and [[empathy]] (all of which are reduced in depressive mood disorders) and regulates the [[limbic system]].

* Behavioral [[irritability]] and [[aggression]]: a 2012 observational analysis of subjects of an earlier study found a strong relation between dietary trans fat acids and self-reported behavioral aggression and irritability, suggesting but not establishing causality.

* Diminished [[memory]]: In a 2015 article, researchers re-analyzing results from the 1999-2005 UCSD Statin Study argue that "greater dietary trans fatty acid consumption is linked to worse word memory in adults during years of high productivity, adults age <45".

* [[Acne]]: According to a 2015 study, trans fats are one of several components of [[Western pattern diet]]s which promote acne, along with [[carbohydrate]]s with high [[glycemic load]] such as [[white sugar|refined sugars]] or [[refined grains|refined starches]], [[milk]] and dairy products, and [[saturated fat]]s, while [[omega-3 fatty acid]]s, which reduce acne, are deficient in Western pattern diets.

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====Biochemical mechanisms====

The exact [[biochemistry|biochemical]] process by which trans fats produce specific health problems are a topic of continuing research. Intake of dietary trans fat perturbs the body's ability to metabolize [[essential fatty acid]]s (EFAs, including [[Omega-3 fatty acid|omega-3]]) leading to changes in the phospholipid fatty acid composition of the arterial walls, thereby raising risk of coronary artery disease.

Trans double bonds are claimed to induce a linear [[conformational isomerism|conformation]] to the molecule, favoring its rigid packing as in [[atheroma|plaque]] formation. The geometry of the ''cis'' double bond, in contrast, is claimed to create a bend in the molecule, thereby precluding rigid formations.

Trans fats are processed by the [[liver]] differently than other fats. They may cause [[liver function|liver dysfunction]] by interfering with delta 6 [[desaturase]], an [[enzyme]] involved in converting essential fatty acids to [[arachidonic acid]] and [[prostaglandin]]s, both of which are important to the functioning of cells.

====Natural "trans fats" in dairy products====

Some ''trans'' fatty acids occur in natural fats and traditionally processed foods. [[Vaccenic acid]] occurs in breast milk, and some [[isomers]] of [[conjugated linoleic acid]] (CLA) are found in meat and dairy products from [[ruminant]]s. Butter, for example, contains about 3% trans fat.

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In 2008 a meta-analysis found that all trans fats, regardless of natural or artificial origin equally raise LDL and lower HDL levels. Other studies though have shown different results when it comes to animal-based trans fats like conjugated linoleic acid (CLA). Although CLA is known for its anticancer properties, researchers have also found that the cis-9, trans-11 form of CLA can reduce the risk for [[cardiovascular disease]] and help fight inflammation.

Two Canadian studies have shown that vaccenic acid, a TFA that naturally occurs in dairy products, could be beneficial compared to hydrogenated vegetable [[shortening]], or a mixture of pork lard and soy fat, by lowering total LDL and triglyceride levels. A study by the US Department of Agriculture showed that vaccenic acid raises both HDL and LDL cholesterol, whereas industrial trans fats only raise LDL with no beneficial effect on HDL.

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====Official recommendations====

In light of recognized evidence and scientific agreement, nutritional authorities consider all trans fats equally harmful for health and recommend that their consumption be reduced to trace amounts. In 2003, the WHO recommended that trans fats make up no more than 0.9% of a person's diet and, in 2018, introduced a 6-step guide to eliminate industrially-produced trans-fatty acids from the global food supply.

The [[United States National Academy of Sciences|National Academy of Sciences]] (NAS) advises the U.S. and Canadian governments on nutritional science for use in public policy and product labeling programs. Their 2002 ''Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids'' contains their findings and recommendations regarding consumption of trans fat.

Their recommendations are based on two key facts. First, "trans fatty acids are not essential and provide no known benefit to human health", whether of animal or plant origin. Second, given their documented effects on the LDL/HDL ratio, the NAS concluded "that dietary trans fatty acids are more deleterious with respect to coronary artery disease than saturated fatty acids". A 2006 review published in the [[New England Journal of Medicine]] (NEJM) that states "from a nutritional standpoint, the consumption of trans fatty acids results in considerable potential harm but no apparent benefit."

====Regulatory action====

{{main | Trans fat regulation}}

In the last few decades, there has been substantial amount of [[trans fat regulation|regulation]] in many countries, limiting trans fat contents of industrialized and commercial food products.

====Alternatives to hydrogenation====

The negative public image and strict regulations has led to interest in replacing partial hydrogenation. In [[fat interesterification]], the fatty acids are among a mix of triglycerides. When applied to a suitable blend of oils and saturated fats, possibly followed by separation of unwanted solid or liquid triglycerides, this process could conceivably achieve results similar to those of partial hydrogenation without affecting the fatty acids themselves; in particular, without creating any new "trans fat".

Hydrogenation can be achieved with only small production of trans fat. The high-pressure methods produced margarine containing 5 to 6% trans fat. Based on current U.S. labeling requirements (see below), the manufacturer could claim the product was free of trans fat. The level of trans fat may also be altered by modification of the temperature and the length of time during hydrogenation.

One can mix oils (such as olive, soybean, and canola), water, [[monoglyceride]]s, and fatty acids to form a "cooking fat" that acts the same way as trans and saturated fats.

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===Omega-three and omega-six fatty acids===

{{main|Omega-3 fatty acid|Omega-6 fatty acid}}

The [[Omega-3 fatty acid|ω−3 fatty acids]] have received substantial attention. Among omega-3 fatty acids, neither long-chain nor short-chain forms were consistently associated with breast cancer risk. High levels of [[docosahexaenoic acid]] (DHA), however, the most abundant omega-3 [[polyunsaturated fatty acid]] in erythrocyte ([[red blood cell]]) membranes, were associated with a reduced risk of breast cancer. The DHA obtained through the consumption of polyunsaturated fatty acids is positively associated with cognitive and behavioral performance. In addition, DHA is vital for the [[grey matter]] structure of the human brain, as well as retinal stimulation and [[neurotransmission]].

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===Interesterification===

Several experimental studies in humans found no statistical difference on fasting blood lipids between a diet with large amounts of IE fat, having 25-40% C16:0 or C18:0 on the 2-position, and a similar diet with non-IE fat, having only 3-9% C16:0 or C18:0 on the 2-position. A negative result was obtained also in a study that compared the effects on blood [[cholesterol]] levels of an IE fat product mimicking [[cocoa butter]] and the real non-IE product.

A 2007 study funded by the Malaysian Palm Oil Board claimed that replacing natural [[palm oil]] by other interesterified or partially hydrogenated fats caused adverse health effects, such as higher [[low-density lipoprotein|LDL]]/[[high-density lipoprotein|HDL]] ratio and [[plasma glucose level]]s. However, these effects could be attributed to the higher percentage of saturated acids in the IE and partially hydrogenated fats, rather than to the IE process itself.

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===Role in disease===

{{Main|Hypertriglyceridemia}}

In the human body, high levels of triglycerides in the bloodstream have been linked to [[atherosclerosis]], [[Coronary heart disease|heart disease]]

and [[stroke]]. However, the relative negative impact of raised levels of triglycerides compared to that of LDL:HDL ratios is as yet unknown. The risk can be partly accounted for by a strong inverse relationship between triglyceride level and HDL-cholesterol level. But the risk is also due to high triglyceride levels increasing the quantity of [[Low-density lipoprotein#LDL size patterns|small, dense LDL particles]].

=== Guidelines ===

<div class="noprint">[[File:Blood values sorted by mass and molar concentration.png|thumb|450px|[[Reference ranges for blood tests]], showing usual ranges for triglycerides (increasing with age) in orange at right.]]</div>

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The [[National Cholesterol Education Program]] has set guidelines for triglyceride levels:

! colspan=2 | Level

! rowspan=2 | Interpretation

! ([[Milligram|mg]]/[[Decilitre|dL]])

! ([[Mole (unit)|mmol]]/[[Litre|L]])

| Normal range&nbsp;– low risk

| Slightly above normal

| Some risk

| 500 or higher

| Very high&nbsp;– high risk

These levels are tested after [[fasting#Medical application|fasting]] 8 to 12 hours. Triglyceride levels remain temporarily higher for a period after eating.

The AHA recommends an optimal triglyceride level of 100{{nbs}}mg/dL (1.1{{nbs}}mmol/L) or lower to improve heart health.