The other fat science

I was recently spurred to review the polyunsaturated fatty acid story, also known as the omega stuff, by an online acquaintance, David Brown, who is a maven on this subject. He is a "maven" in the Malcolm Gladwell sense of the word, from The Tipping Point. I guess I am a maven too, a more generalized fat science maven.

David Brown referred me to several references 1,2,3 to which I found a 4th from the fat science library that I had read many years ago. I thought I had put this subject to bed back then. I'm not sure this new appreciation changes that bed very much.

The most important and succinct summery of this other fat science is Professor Hulbert's commentary from 2021. (1) Anthony John Hulbert, PhD, DSc, was a professor in Science, Medicine and Health at the University of Wollongong, New South Wales, Australia. He is bigger than a maven since he is a professional and primary researcher as well as evangelist on this subject.

The first point he makes and the biggest dealio of all is that fat science isn't just about the calories and energy stores of fats in our bellies that most people are most obsessed about. There is another half of fat science that is about the fats that go to make up the membranes around all the cells in your body as well as the membranes inside those cells like the wall of the nucleus that houses your DNA and the membrane around the mitochondria that make the energy needed to power your life. This under-appreciated type of fat is probably more important fat science than the other fat we worry about since it is more important for metabolism, health, nutrition and longevity. This other fat science actually predates the evolution of the energy storage fat and represents more of the fat in your body. Indeed the second most fatty rich organ of your body after the yellow fat is the brain.

We are going to need pictures to explain the biochemistry of the fat that makes up the skin of all the cells in the world.

The chemistry of life is based on the carbon atom. It has 4 bonds to connect to other atoms thus:

That makes it seem like things connected to carbon are naturally 90 degrees apart but in 3D carbon atoms actually look more like this:

Then the angle between connections to carbon are actually more like 109.5 degrees but on 2D paper we can approximate the picture by drawing the connections like this:

Fatty acids are long chains of usually 18 to 22 carbons and every vertex represents a carbon like this:

Hydrogen is usually not shown either:

This picture makes it look like they are connected with sticks but more accurately they are more like blobs that are glued together:

The reason fatty acids are acids (acids try to push off protons or hydrogen atoms) is because at one end they have this business:

The acid end with the oxygen =O and hydroxy HO- is reactive and is kind of a handle for hooking up to other stuff and it is water soluble, AKA hydrophilic. The other end of the fatty acid can’t dissolve in water that is to say it is hydrophobic and is called the omega end. Ω

Those are free fatty acids FFA when they float around like that but when 3 of them are attached to a glycine they are called triglycerides and they exist like that in blubber:

These long chains of carbon and hydrogen have beaucoup energy when burned with oxygen to make CO2 and H2O. Therein lies the value of fat in those bubbles packed with triglycerides for energy storage.

But now the other fat science.

The other fat science is based on double bonds between some carbons like this:

But that introduces some other variables like how far from the omega end the first double bond is. It is called omega-3 if it's 3 from the omega end or omega-6 if it's put 6th from the omega end. The other variable is that the double bond can be cis or trans. Cis makes the chain "crooked" and trans keeps the chain "straight.":

^ cis double bonds crooked ^ trans double bonds straight

We have only recently figured out that the trans double bond is pretty bad for your health. The cis omega-3 and cis omega-6 configuration fatty acids are essential. That means they are like vitamins, or essential amino acids for building proteins. Essential here means that your metabolism can't make them. Only plants know how to put in these double bonds in those spots. So you have to eat them or you get into trouble.

https://www.khanacademy.org/science/ap-biology/chemistry-of-life/properties-structure-and-function-of-biological-macromolecules/v/saturated-fats-unsaturated-fats-and-trans-fats

The last pictures are the molecular structure of a soap bubble and a cell wall which is kind of a like an inside out soap bubble wall:

soap bubble

cell wall

A few more things that we can understand without pictures:

- saturated fats only have single bonds between each carbon. Saturated here means "saturated" with hydrogen.

- unsaturated means double bonds.

- monounsaturated means one double bond.

- polyunsaturated means more than one double bond.

- when you mix cis omega 3 and 6 fatty acids in the cell wall the crooked tails make it harder to be packed together and that makes them more liquid at body temperature and things can shift around more easily. Obviously it is really necessary to do what cell walls are busy doing all the time which is keep things separated. Cell walls keep certain things inside the cell separated from other things outside the cell. Proteins embedded in the cell wall also grab and suck in or spit out things like hormones and other signal molecules. Amazing.

That much is understandable, even for me, but then it quickly gets murky when we try to understand what is the proper ratio of omega-3 fatty acids and omega-6 fatty acids you should be eating and how and why.

Both of them are independently essential. You get sick if you never eat omega-3 and omega-6 fatty acids. It also seems demonstrable that you can alter the ratios in your cells' walls of those two omegas - omega-6/omega-3, very quickly by eating plants with different amounts or by eating meat of animals who ate different ratios. Also there seems to be a lot of circumstantial evidence that we have been eating more omega 6 than 3 for a long time and maybe that is causing problems in every organ and system in our bodies. That might make some sense when you realize that every cell in your body has a cell wall and besides being integral to cell walls, omega-6 and omega-3 fatty acids also go to make up myriad immunological and inflammatory signals, for example prostaglandins.

Dr. Hulbert's article outlining the polyunsaturated fat science is fascinating reading that was a lot of revelation to me. At the end he talks about diet and the last sentence teases, "In the opinion of the current author and others, these diet trends are likely to be responsible for the increased incidence of obesity and other modern epidemics of chronic disease, but that is a story for another time." That was 2021. In his 2023 book he goes on to describe the abundant circumstantial evidence for that contention.

It is the contention of Dr Hulbert in his article and in his book that we don't get enough omega 3 unsaturated fats in our diets and that is the source of health evils in modern life. If you eat a ton of omega 6 fatty acids from grains and vegetable oils then you have to eat a ton of omega 3 fatty acids that are more unusual in our diets. Conversely, I guess, if we weren't eating so much omega 6s we wouldn't need to find so much omega 3 to eat.

There is one chapter dedicated to obesity, chapter 6. This I know a little about. He states that the cause of our obesity epidemic must be environmental but that environment is not about gluttony and sloth, and not so much about calories but instead this imbalance of the omegas.

The other chapters lay problems of brain and heart and immunology and allergy and etc., that I know less about, at the feet of this dietary omega imbalance. He even frames the trans fatty acid fiasco as part of this. (page 238)

Peter Attia's podcast #83 with Bill Harris Phd, another professional and primary researcher of the omegas is subtitled, "I don't think [omega-6] is the evil that people think it is. The problem is that we need to get more EPA and DHA (omega-3 fatty acids) in our diet, not necessarily get all hung up on omega-6."

However careful prospective studies of different diets and supplements makes all this fizzle. Maybe we don't need to get too hysterical. It's kind of like the vitamin D craze when everything was caused by low vitamin D intake until they did careful prospective studies. Then only rickets comes from drastically low dietary vitamin D intake. I have only read about rickets in my 45 years of practice. I never saw a case.

Indeed on page 150 of Omega Balance Dr. Hulbert writes, "Enough already! It's too complicated."

My question for professors Hulbert and Harris whenever I get to talk to them is how can we know how much of any turnover of these essential fatty acids is provided by recycling what we already have vs having to eat more? Why isn't that accounting readjusted automatically by your body when there is a relative shortage or imbalance in what you eat? I have asked the same question about dietary protein.

1. Hubert AJ. The under-appreciated fats of life: the two types of polyunsaturated fats. J Exp Biol. 2021 Apr 15;224(8):jeb232538. doi: 10.1242/ jeb.232538. Epub 2021 Apr 22.

2. Hulbert AJ. Omega Balance. 2023 by Johns Hopkins University Press. Baltimore, Maryland 21218

3. https://peterattiamd.com/billharris/December 9, 2019, #83 – Bill Harris, Ph.D.: Omega-3 fatty acids.

The Omega Plan

Motivated as explained above, I recently reread this book and found it to be an easily digested earliest version of the the other fat science. Dr. Artemis Simopoulos still teaches this point of view. She is a pediatrician, like me, and for 9 years chaired the Nutrition Coordinating Committee of the National Institutes of Health and so is steeped in the evidence. Most of all she is Greek and so a childhood consumer of the Mediterranean diet that remains the party line of what kind of whole foods diet we should be eating. (5,6)

The Omega Plan is somewhat dated just since 1998. Number 7 of the otherwise still sound 7 dietary guidelines advice of her omega plan says don't eat trans-fatty acids. That's impossible to do anymore in 2024. Also she still calls the metabolic syndrome by it's earliest name - syndrome X. But the rest of the basic science is still basic and well written. Drink olive oil.

4. Simopoulos AP., Robinson J. The Omega Plan. 1998 by Harper Collins Publishers, New York NY 10022.

5. Kris-Etherton P et al. Lyon Diet Heart Study. Benefits of a Mediterranean-Style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease. Apr 2001 https://doi.org/10.1161/01.CIR.103.13.1823 Circulation. 2001;103:1823–1825

6. Martínez-González, Miguel A.; Salas-Salvadó, Jordi; Estruch, Ramón; Corella, Dolores; Fitó, Montse; Ros, Emilio; PREDIMED INVESTIGATORS (2016-08-01). "Benefits of the Mediterranean Diet: Insights From the PREDIMED Study". Progress in Cardiovascular Diseases. 58 (1): 50–60. doi:10.1016/j.pcad.2015.04.003. hdl:10230/25644. ISSN 1873-1740. PMID 25940230.

One further item in this debate to add to your adventure:

Dueling reports about omega-3 fats

A recent New England Journal of Medicine (NEJM) has dueling reports about the possible benefit of omega-3 fats. (7-10) During the past 10 years the number of people taking fish oil supplements has increased by a factor of 10. This is part of a more general craze whereby more than half of us are taking dietary supplements, none of which have been shown to do any good. In the case of fish oils this is because of earlier observational reports that people who eat fish have fewer heart attacks and strokes. But this carefully masked prospective study of fish oil supplements shows that it did't prevent cardiovascular disease or death when compared with placebo. (7)

Fish oils have of cocktail of different omega-3 fats that are generally credited as working because of their omega-3ness. But the same issue of NEJM has another report that used one particular omega-3 fat, called eicosapentanoic acid (EPA). They showed that EPA supplements did indeed cause about a 25% reduction in death and disease from cardiovascular stuff but not death overall in 8179 people who already had CV disease or risk factors for it.

It was felt that how fish oils might help was by reducing your blood triglyceride levels. Remember that in the hierarchy of your lipid profile (LDL cholesterol (bad cholesterol), HDL (good cholesterol) and triglycerides, the triglycerides are the least important culprit in CV disease. In this study the levels of triglycerides didn't seem to correlate with the benefit of the EPA. (8) So if EPA helped anything it must be for some other reasons.

But not so fast. There turns out to be a glitch in this study that may vitiate the benefits conclusion. Read ref. 11 if you want to hear the gory details.

This is good because we seem to be depleting the oceans of fish to eat.

By the way vitamin D supplements did't help CV disease either and neither did vitamin D or fish oils prevent cancer in these two studies.

7. Manson JAE. et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 2019;380:23-32.

8. Bhatt DL. et al. Cardiovascular risk reduction with eicosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.

9. Kastellein JJ, AStroes ESG. FISHing for the miracle of eicosapentinoic acid. N Engl J Med 2019;380:89-90.

10. Keaney JF, Rosen CJ. Vital signs for dietary supplementation to prevent cancer and heart disease. N Engl J Med 2019;380:91-3.

11. https://peterattiamd.com/a-new-analysis-of-reduce-it-benefits-of-omega-3s-vs-harm-from-placebos/