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The most underrated dietary factor to focus on is shifting dietary fat intake away from long-chain saturated fats, toward short and medium-chain saturated fats, and toward odd-chain saturated fats For now it feels like I'm the only one talking about chain length THREAD //
There are different nuances to this, but the biggest point I've argued is that we now consume much more palmitic acid (a 16 carbon long chain saturated fat) than our ancestors The same is true for myristic acid (14 carbons) as well Palmitic acid in particular is problematic
The main reason for this is its accumulation in cell stress When people talk about free fatty acids, visceral fat synthesis, and insulin resistance, they all boil down to high free palmitic acid levels in the cell cytosol
In cases of energy surplus or impaired metabolism, excess acetyl-coa is carboxylated by ACC into another intermediate called malonyl-coa Fatty acid synthase, another enzyme implicated in various diseases, including cancer, drives conversion of malonyl-coa into palmitic acid
When a human or animal is obese, the majority of the fatty acids they create are in the form of palmitic acid This is also the case in industrial agriculture, where cows are fed grains, low fiber diets, and given antibiotics, in order to make them store more carbohydrates as fat
This results in modern meat containing previously unheard of levels of palmitic acid and far more fat in general vs wild meat This is why I'm so adamant about eating wild game like bison, elk, venison, and boar, instead of modern industrial meat
Palmitic acid and other long-chain saturated fats drive cell stress through several mechanisms Free PA blocks downstream signals from insulin receptors, and this is now thought to be the primary mechanism behind insulin resistance While MUFAs like oleic acid are protective
This is also implicated in general inflammation and cytokine release, via palmitic acid's activation of TLR4 receptors in the gut and brain Palmitic acid enhances response to bacterial endotoxin <a target="_blank" href="https://www.nature.com/articles/s41598-018-29735-6" color="blue">nature.com/articles/s4159…</a> And contributes to neural stress and brain inflammation <a target="_blank" href="https://journals.physiology.org/doi/abs/10.1152/physiol.2023.38.S1.5732794" color="blue">journals.physiology.org/doi/abs/10.115…</a>
Now this is definitely an issue in obesity, in which case fatty acid synthase enzymes are over-activated, and free palmitic acid is being liberated into organs like the brain, liver, and pancreas But what are the impacts of dietary long-chain saturated fat intake?
It turns out there are a few different avenues of research on this question This study found that the MUFA oleic acid improved resting total daily energy expenditure, while palmitic acid lowered it <a target="_blank" href="https://www.sciencedirect.com/science/article/pii/S0002916523295623" color="blue">sciencedirect.com/science/articl…</a>
This study points out a number of problems in palmitic acid metabolism <a target="_blank" href="https://www.lipidjournal.com/article/S1933-2874(23)00229-5/fulltext" color="blue">lipidjournal.com/article/S1933-…</a> - Palmitic acid synthesis is increased in low-fat diets, so avoiding fat is not a good solution - Palmitic acid from food does influence circulating levels - The increase in heart disease seen in RCTs and observational studies in saturated fat intake are mostly attributable to long-chain saturated fats and their ability to increase LDL particle count and skew LDL/HDL ratio - Palmitic acid has a FAR greater impact when obesity and insulin resistance are already present, as more PA is found in the "free" form in these individuals
However, this article is another good overview of many sides of this question <a target="_blank" href="https://www.frontiersin.org/articles/10.3389/fnut.2022.861664/full" color="blue">frontiersin.org/articles/10.33…</a> It makes several good points: - PA and myristic acid both negatively affect HDL/total cholesterol ratio, and increase LDL particle number, though this will have far worse effects when combined with other risk factors - The body desaturates some dietary palmitic acid to MUFA as a protective mechanism - Many studies highlight the impact of PA by swapping it with things like omega-3 fats which would normally be protective against free fatty acids - Replacing palmitic acid with PUFA will skew PUFA intake too high, causing problems of its own
Lastly, both palmitic acid and myristic acid have been shown to directly elevate apoB, the best overall predictor of heart disease since it's a proxy for LDL particle count <a target="_blank" href="https://www.ahajournals.org/doi/pdf/10.1161/01.ATV.14.4.567" color="blue">ahajournals.org/doi/pdf/10.116…</a>
Remember that heart disease is the number one cause of death in the United States, and increased LDL particle count and apoB is the closest predictor of mortality, so this is the biggest cause for concern here I wrote a previous thread on this topic for those interested: <a target="_blank" href="https://twitter.com/photobiogenesis/status/1495502499024982025" color="blue">x.com/photobiogenesi…</a>
So where does this leave us? I'm not in favor of replacing palmitic acid and myristic acid with omega-6 or omega-3 PUFA, as the amount you'd need to swap would be excessive Our bodies need fairly limited amounts of PUFA, and the O3:O6 ratio needs to be balanced
We could also swap some long-chain SFAs for carbohydrates, and this seems to be neutral or mildly beneficial as far as I can tell However there's also a third option... focusing instead on saturated fat sources rich in short and medium chain fats rather than long chain fats!
This is the approach I've landed on personally Let's look at some of the benefits of short and medium chain length These include fats like lauric, capric, caprylic, caproic, and butyric acid, all of which have very interesting effects
Lauric acid is the most abundant in food It only slightly raises LDL while significantly improving HDL, so it creates a more favorable ratio In general, the shorter the chain length the less a fat raises LDL particle count (the exception is stearic acid C18 which is neutral) <a target="_blank" href="https://openheart.bmj.com/content/3/2/e000467" color="blue">openheart.bmj.com/content/3/2/e0…</a>
Medium and short chain length fats also bypass the carnitine shuttle and enter mitochondria more quickly MCFs increase metabolic rate in the short term, increase levels of acetyl-coa, produce a thermogenic effect, and even elevate circulating ketones without protein catabolism
Short chain fats like butyrate can either be acquired from food, or produced by gut bacteria digesting soluble fiber Dairy products are high in butyrate when ruminants are grassfed and eating a high fiber diet Butyrate has potent anti-inflammatory effects, and promotes neuroplasticity by acting as an HDAC inhibitor