Fats. The Good, the Bad, and the Ugly
Lipids are:
- Biomolecules that contain fatty acids or a steroid nucleus
- Soluble in organic solvents, but not in water
- Named for the Greek word lipos, which means “fat”
- Extracted from cells using organic solvents
Some lipids contain fatty acids:
- Waxes
- Fats and oils (triacylglycerols)
- Phospholipids
- Prostaglandins
And some do not. Steroids, for example, are lipids that do not contain fatty acids (hydrophobic and insoluble).
Dietary Fats and Cardiovascular Disease
According to the American Heart Association, Cardiovascular disease (CVD) is the leading cause of death globally, accounting for 17.3 million deaths per year. Today, there is much confusion about good fats, bad fats, or if fat in the diet matters at all. The most recent AHA presidential advisory statement (Circulation. 2017) highlights data from randomized controlled trials that show that when the intake of dietary saturated fat is lowered and replaced with polyunsaturated vegetable oil, CVD is reduced by about 30%. This result is similar to the levels of reduction that can be achieved by statin treatment. That is a powerful statistic – and good evidence that – yes, food is really medicine. The mechanism by which this works is that when saturated fat is replaced with unsaturated fat, we lower the production of low-density lipoprotein cholesterol, a cause of atherosclerosis. Which brings us to a discussion of the current trend of:
Coconut oil has a saturated fat content of 90 percent. Now, how could this possible mesh with our current understanding of lipid biochemistry and cardiovascular disease? The results of a survey published in July 2016 showed that 72 percent of people polled in the United States thought coconut oil was healthful. At the same time only 37 percent of nutritionists polled would agree with that statement. Let’s consider the facts about coconut oil in light of what we understand about lipids.
Coconut oil contains 2.6 percent fewer calories than other fats. According to the United States Department of Agriculture (USDA) National Nutrient Database, one tablespoon, or 15 milliliters (ml) of coconut oil contains:
- 120 calories
- 0 g of protein
- 14 g of fat, of which 12 g is saturated, 1 g is monounsaturated, and 0.5 g is polyunsaturated
- 0 milligrams (mg) of cholesterol
It provides no fiber and little to no vitamins or minerals.
Coconut oil has an unusually high amount of medium-chain triglycerides (MCTs). These are harder for the body to convert into stored fat and easier to burn off than long-chain triglycerides (LCTs). See the metabolic pathway below to understand why that might be true. Note that most of the benefits claimed for coconut oil are likely due to the high MCT content.
Now consider the claims I found during a recent tour of our friendly local Wikipedia entry:
Due to its high levels of saturated fat, the World Health Organization, the United States Department of Health and Human Services, United States Food and Drug Administration, American Heart Association, American Dietetic Association, British National Health Service, British Nutrition Foundation, and Dietitians of Canada advise that coconut oil consumption should be limited or avoided.
As you can see by clicking on the links above, this is a well documented and verified statement. I have upgraded my opinion of Wikipedia considerably. Can we reconcile the positive health claims for coconut oil with the warnings against high level of saturated fat? Let’s anchor our evaluation of the claims on both sides of the debate with a little nutritional biochemistry knowledge.
You might recall from class that we discussed the way in which some MUFA might be healthy. A brief review. There is a positive correlation between cardiovascular disease and total fat, saturate fatty acids, cholesterol, trans fat, and a negative correlations with MUFA and PUFA. Mammals, however, have enzymes to introduce doubles bonds (desaturate) some MUFA at C4, C5, C6 or C9. The example I used in class was stearic acid (18:0). This is a saturated fatty acid that has been shown to reduce both total cholesterol and LDL levels. Why? Well, the explanation is that stearic acid (18:0) can undergo desaturation and become oleic acid (18:1Δ9), and oleic acid is the MUFA that makes olive oil a “good” fat.
So, 18:0 can be desaturated to 18:1 Δ9 by our endogenous enzyme system – and that is a good thing. Now, look at the approximate concentration of fatty acids in coconut oil :
- Caprylic acid, saturated (C8:0) 7%
- Decanoic acid, saturated (C10:0) 8%
- Lauric acid, saturated (C12:0) 48%
- Myristic acid, saturated (C14:0) 16%
- Palmitic acid, saturated (C16:0) 9.5%
- Oleic acid, monounsaturated (C18:1) 6.5%
- Other 5%
Myristic acid and lauric acid can undergo desaturation similar to that of stearic acid to create two rather rare medium chain MUFAs (myristoleic acid, C14:1, and lauroleic acid, C12:1). There is some peer-reviewed, but limited, evidence that myristic acid and lauric acid fats raise HDL. However, the same studies show increases in total cholesterol as well. This probably contributes to what must be our final conclusion about the health benefits of coconut oil – that the only thing we know conclusively at this point about about the link between CVD and coconut oil is that the relationship is complex and non-conclusive.
Final “food for thought” about medium chain triglycerides (MCT) and medium chain fatty acids (MCFA). One of the studies that made people think coconut oil might be healthful was led by Dr. Marie-Pierre St-Onge, of Columbia University. Her research team published a 2008 study of 31 men and women who consumed MCT oil or olive oil during a 16-week weight loss program. This research concluded that MCT oil, of which coconut is an example, is processed differently in the body than other oils.
Let’s look at the MCT metabolic pathway. Note the by-pass of the carnitine shuttle system:
(Although I like this figure from Nutrition Review .org (https://nutritionreview.org/2013/04/medium-chain-triglycerides-mcts/), please be aware that the site is a front for a nutritional supplement company. Although the research cited is peer-reviewed, the accompanying article veers into opinion as opposed to fact)
Since MCFAs do not require the help of carnitine, they cross the mitochondrial membrane very rapidly compared to long chain fatty acids (LCFAs). This can result in an excess of acetyl-coA. A “flood” of acetyl-coA can swamp the TCA cycle and ultimately result in the production of ketones. Scientists attribute any energy boost associated with the consumption of MCTs to the rapid formation of ketone bodies. You will recall the energetics of ketone production and oxidation to make ATP differs from that of glucose oxidation and production of ATP. The end result is that MCTs provide approximately 10% fewer calories than LCTs – 8.3 calories per gram for MCTs versus 9 calories per gram for LCTs.
The St-Onge (2018) paper concluded that: “Our results show that MCT consumption leads to comparable effects on CVD risk factors as an equal amount of olive oil, an oil considered to have beneficial health effects.” The popular (not scientific) interpretation of this experimental outcome has been that, because MCTs can have a positive effect on HDL and total cholesterol levels, coconut oil must be healthful. However, St-Onge believes that their results have been interpreted too liberally to support the consumption of coconut oil, especially as their study used a special oil that was 100-percent MCT – not coconut oil.
Let’s consider this outcome in practical terms. Most coconut oils are only 13 to 14 percent MCT. To replicate the results produced by the St-Onge research group a person would have to eat 150 grams, or 10 tablespoons, of coconut oil each day. Regardless of dietary source, consuming that volume of oil per day is not healthy. Consider that the American Heart Association (AHA) recommends limiting all saturated fats to no more than 5-6 percent of total calories. This includes fats from tropical oils, whether or not they contain MCTs. The 2015-2020 Dietary Guidelines for Americans are a little less strict, recommending no more than 10 percent of total calories come from saturated fat.
Well. Wow.
There are other potential problems with broad application of this research. In particular, many studies supporting coconut oil have been done over short periods of time, with few participants, and with results not significant enough to prove any benefit to coconut oil consumption. Other studies, some of the most frightening, cannot be verified at all and make wildly inappropriate claims about benefits to people suffering from potentially terminal disease states, including cancer and HIV. Many of the claims you can find on the internet for coconut oil rank right up there with the conspiracy theory claims about Aspartame. These substances may, or may not, be healthy. Either way, we need to stay within in the realm of scientific fact and metabolic reality when evaluating nutritional claims.
Don’t tell Trader Joe’s this, but the jury is still out – the scientific data regarding the use of SFA loaded coconut oil is not yet conclusive in any way for the effects on CVD. However, the results of research supporting a dietary switch to unsaturated fatty acids (PUFA) are quite reliable.
Medium-chain triglycerides (MCTs):
are fats that are made in a lab from coconut and palm kernel oils, which differs from typical dietary fats (long-chain triglycerides).
MCTs are a fat source for people who cannot tolerate other types of fats. These fats might also improve weight loss since the body can more easily break MCTs down into molecules called ketone bodies. These ketone bodies can be used for energy.
Fatty Acid Oxidation occurs mainly in the mitochondria and involves a series of events that result in fatty acid turning into acetyl- CoA. Then this goes through Beta oxidation which results in ATP being produced. Fat is also the major source of energy in the body.
Chylomicrons is the product of re-esterification and repackaging of dietary lipids through hydrolysis. Chylomicrons are responsible for transporting dietary triglyceride from the GI to the liver, adipose tissue, and muscle. It carries dietary triglycerides more than it does cholesterol esters.
The current understanding of fatty acids is somewhat convoluted, but this may be due to the fact that there still is a great deal to learn about them. It is evident that MCT are favored in certain contexts, but less ideal in others. Since this pathway does not need carnitine, and contributes to the ketone state of the cell and therefore the body, I would imagine that an increased intake of MCT may be correlated to a continual fat burning state.
High-density lipoprotein (HDL) collect free cholesterol from other lipoproteins and cells, and send it to liver: “reverse transport” of cholesterol from cells to the liver. In liver, cholesterol is used to synthesize bile acids.
Low-density lipoprotein (LDL) is derived from VLDL, and functions to carry endogenous cholesterol to the tissues. LDL is still necessary in the body, but commonly known as “bad” cholesterol, because elevated LDL levels are associated with individuals who are overweight or obese.
Saturated fatty acids contain only single C-C bonds and are closely packed. They also have high melting points and are solid at room temperature. On the other hand, unsaturated fatty acids have one or more cis C=C bond which create kinks in the chains. They are unable to pack together closely and have low melting points. They are liquids at room temperature. Trans fats have trans double bonds; they behave like saturated fatty acids inside the body. Studies have found trans fats to raise LDL-cholesterol and lower HDL-cholesterol.
In the small intestine bile emulsifies fats into micelles that enable them to mix with water in the lumen and increase their surface area so pancreatic lipase and cholesterol lipase can act. The micelle then diffuse across the unstirred water layer where it breaks up into its lipid products to cross membrane. Bile salts stay in the lumen until it reaches the ileum where it can be reabsorbed and enter enterohepatic circulation. Short and medium chain fatty acids go directly into the portal vein. After being Reesterified the products of the micelle are wrapped into chylomicrons where they are released by exocytosis into the lymphatic system.
Very low density lipoprotein (VLDL) transports mostly triglyceride, some cholesterol, from liver to periphery. Carries endogenous triglyceride.
VLDL is similar to LDL cholesterol, but LDL mainly carries cholesterol to your tissues.
Lipids are biomolecules that contain fatty acids or a steroid nucleus. Lipids are soluble in organic solvents, but not in water. They are extracted from cells using organic solvents. Waxes, fats and oils (triacylglycerols), phospholipids, and prostaglandins are the types of lipids containing fatty acids. On the other hand, steroids (hydrophobic and insoluble) are types of lipids that do not contain fatty acids.
In the mucosal phase of lipid absorption, there are 4 steps. First, digestive products diffuse across the brush border membrane, then lipid products (that are not short/medium chain fatty acids) must be reesterified, next chylomicrons (a lipoprotein that carries exogenous dietary lipids) are synthesized, and finally, chylomicrons are released from the cell to the lymphatic system.
Endothelium in a capillary bed injury- picture explanation:
1) An increase in blood pressure causes cracks in the endothelium, and the body sees this as an injury.
2) Phospholipids are then turned into pro-inflammatory prostaglandins and platelets.
3) Monocytes enter and undergo mitosis due to signal and turn into macrophages.
4) LDL cholesterol is sent to fix the membrane.
5) Foam cells are macrophages that have been sent to clean up the LDL but slip into cracks and forms plaque.
6) Plaque is built up foam cells, can break off and this all happens again.
7) This is an example of positive feedback.
Lecithin and cephalin are phospholipids abundant in brain and nerve tissues. They are found in egg yolk, wheat germ, and yeast. Lecithin in egg yolk allows it to function as an emulsifying agent. It is used in cooking to blend together fats and water soluble ingredients. This is because the polar part can interact with mater and the non polar part mixes with fats.
Intermediate-density lipoproteins (IDLs) are a type of lipoprotein that carries endogenous cholesterol. IDLs only exist for a short amount of time. They are derived from VLDL in the capillaries of adipose tissue and muscle after the extraction of triglycerides by LPL in the capillary beds.
Apolipoproteins are the protein components of lipids. These are crucial in stabilizing lipoproteins, as well as acting as “markers” for the lipoproteins. With this, the type of apolipoprotein defines the lipoproteins identity. Apolipoproteins likewise play a role in the activity of specific enzymes.
Carnitine is a quaternary ammonium compound that is involved with metabolism in most mammals and plants. It is synthesized from lysine and methionine. Its main function is to help transport long-chain fatty acid through inner mitochondrial membrane in order to be oxidized for energy production. It can be easily obtain from meat consumption.
Triacylglycerol Synthesis is the mechanism that forms triaglycerols which are fatty acids that are stored for future use. These are found in all cells, but mainly adipocytes, and stored in lipocytes that expand as TAGs are added. Also, the fatty acids that are present in TAGs are maily saturated.
Apolipoproteins are the protein components of lipoproteins. Apolipoproteins are able to give lipoproteins their identities, using the letters A to E with subclasses. These identities serves as marker to be recognized in both endogenous and exogenous pathways. They also function to stabilize lipoproteins and the activity of certain enzymes
transamination:
the transfer of an amino group from an amino acid to a keto acid produces and a new amino acid and a new keto acid
it is the link between carbohydrates and AA metabolism
The most active aminotransferases:
– Alanine aminotransferase (ALT)
– Aspartate Aminotransferase (AST)
distinguishing transamination and deamination:
Transamination:
– Does not get rid of NH3
– Only transfer from one molecule to another
Deamination:
– To get rid of NH3 from body
– First the amino acid transaminates to glutamate
The beginning of the Urea Cycle:
Because it’s harmful to have an excess amount of ammonia (NH4) in the body due to its toxicity, we need to excrete it by moving it to the liver where it is convert to urea. Urea is a non-toxic way to get rid of nitrogen (2N) from the body. This all starts in the mitochondria, with carbamoyl-p combining with ornithine (which is similar to OAA, we need enough to continue the cycle). This forms citrulline and leaves the mitochondria to the cytosol. This is converted to arginino-succinate, then splits into fumerate (which goes to the TCA) and arginine. Next it goes back to the starting product of ornithine, which can combine with carbamoyl-p to keep the cycle going.
OMEGA-6 Fatty Acids – a family polyunsaturated fatty acids that have a final carbon-carbon double bond in the n-6 position in common (the sixth bond counting from the methyl end). Found in poultry, eggs, nuts, sesame seeds, cereals, durum wheat, whole grain breads, pumpkin seeds, vegetable oils. Includes linoleic acid, gamma-linolenic acid, calendic acid, eicosadienoic acid, Dihomo-gamma-linolenic acid, arachidonic acid, docosadienoic acid, adrenal acid, osbond acid, tetracosatetraenoic acid, and tetracosapentaenoic acid.
OMEGA-3 Fatty Acids – Polyunsaturated fatty acids that are characterized by a double bond, there toms from the terminal methyl group. The three types involved in human physiology are a-linolenic acid (ALA), eicosapentaeonic acid (EPA), and docosahexaenoic acid (DHA). ALA is found in plants such as seeds, nuts, and plant oils, while DHA and EPA are found in algae and fish, including oils. ALA is not synthesized or made by our bodies. DHA in the form of lysophosphatidylcholine is transported into the brain by a membrane transport protein, MFSD2A, which is exclusively expressed in the endothelium of the blood–brain barrier.
Essential fatty acids are those that the body cannot produce and need to be obtained from diet. There are 9 essential fatty acids – phenylalanine, valine, threonine, methionine, tryptophan, histidine, isoleucine, leucine, and lysine. Complete proteins contain all 9 and include items such as beef, poultry, fish, eggs, dairy, soy, quinoa and buckwheat.
Endopeptidases are enzymes that act on peptide bonds within the peptide or protein. The two that are used in protein digestion and absorption are Trypsin and Chymotrypsin.
Exopeptidases cleave off amino acids by acting on peptide bonds and the C-terminal of the protein or peptide. Carboxypeptidase A acts on most amino acids, with the exception of Lysine and Arginine. Carboxypeptidase B acts on Lysine and Arginine.
Cholesterol can be produced in the body. Acetyl CoA is the starting product and then, through the use of HMG CoA reductase and HMG CoA synthase, gets turned into mevalonate. Mevalonate can then be turned into cholesterol. HMG CoA reductase and synthase are regulated on the transcriptional level .
c-11 is an apolipoprotein responsible for signalling to LPL to release free fatty acids in the exogenous pathway (chylomicron).
C-11 is an apolipoprotein responsible for signalling to LPL to release free fatty acids in the endogenous pathway (VLDL).