Mauritius - When the effects of saturated fat replacement failed to conform to the modelling, no-one cared.

There may be no country in the world in which a suggested limit on saturated fat has not been followed by a relatively rapid increase in the incidence of diabetes and obesity.

Of course this is a matter of observation not experiment, but so is most of the evidence that various dietary guidelines organizations have relied on over the years.

 

A particularly egregious case seems to have occurred in Mauritius, after the Mauritian Government changed the fat content of ration oil, a cheap cooking oil used by most of the population, by decree. In 1987 it had been 75-100% (median 87.5%) palm oil, with (by then) some soybean oil – overnight this was changed to 100% soybean oil. This change was based on predictions from the research of Ancel Keys into heart disease, in particular the 7 Countries study and the intervention in East Finland.

This took PUFA intakes (almost all linoleic acid) to 8.6%E for men and 8.8%E for women, and lowered SFA intakes to 7%E and 7.5%E respectively. These were, as reported, not high fat diets, and it may be relevant that Mauritius is a sugar-producing nation.[1,2]

 5 years later, in 1992, researchers, including experts from Finland and the WHO, measured the changes in fat intake and cholesterol in the Mauritian population, focusing on Hindu Indians.

 

"In the 5-year survey of lipids and other biomarkers, mean population serum total cholesterol concentration fell appreciably from 5.55 mmol/l to 4.7 mmol/l (P<0.001). The prevalence of overweight or obesity increased, and the rates of glucose intolerance changed little."[1]

 

However, in a letter to the BMJ, N Chandrasekharan, a consultant chemical pathologist and Kalyana Sundram, senior research officer of the Palm Oil Research Institute of Malaysia disputed these findings -

 "On the purported fall in serum cholesterol concentration from 5.7 mmol/l in 1987 to 4.6 mmol/l in 1992, it is not evident whether the samples were from the same subjects.

The data for 1992 on the per caput fat intake of 56.2 g per day based on a 24 hour dietary recall is a far cry from the 73.7 g reported by the Food and Agriculture Organisation. The figures for edible oil intake seem erroneous. In 1987 palm oil accounted for only 27.5% of the edible oils consumed and its saturated fatty acids contributed 1.89% of the total energy intake and this fell to 0.33% in 1992."[3]

 

However, we have previously found FAO fat consumption estimates to be unreliable, overestimating NZ butter consumption in recent years by a factor of 4. And Chandrasekharan and Sundram’s letter contains this statement:

 "Although we are also concerned about the need to reduce the prevalence of non­communicable diseases in Mauritius, we disagree on the kind of simplistic thinking and draconian measures advocated."[3]

 

In other words, whatever the effect on fat intakes or cholesterol, the change was a radical one. It put more linoleic acid into the Mauritian food supply, and as in other places, the change in mandated fats would have been accompanied by voluntary changes along the same lines. We may doubt whether cholesterol levels changed, but not that people began to consume more soybean oil.

 So what happened? The 1987 intervention included several good ideas – exercise more, smoke less, drink less – as well as less certain ones – eat less salt, eat less saturated fat and more soybean oil.

 However, it seems unlikely that CVD went down – circulatory mortality as a percentage of mortality increased after 1987. [4]

 "Over 1981–2004 the proportion of circulatory disease mortality rose from 44% to 49% in males, and from 46% to 57% in females."

 

Mauritius is now #2 in the world for diabetes mortality. However, a coding change in 2004 meant that much of what had been recorded as circulatory disease mortality was shifted to diabetes mortality. What we do know is that diabetes prevalence increased, as has incidence of pre-diabetes.

 "The prevalence of Type 2 diabetes increased significantly during the period studied, from 12.8% in 1987, to 15.2% in 1992, and 17.9% in 1998."[5]

 

Note that this contradicts the 1992 claim – by some of the same authors – that “the rates of glucose intolerance changed little” between 1987 and 1992, a discordance not mentioned in the 2002 paper.[1]

 "The age-standardized prevalence of diabetes in 2009 was 22.3% (95% CI 20.0–24.6) among men and 20.2% (18.3–22.3) among women, representing an increase since 1987 of 64 and 62% among men and women, respectively".[6]

 

The Mauritius fat change paper has been cited just 17 times in 25 years, and not one of the citing papers includes any follow up on the consequences of the change there. For example, an AHA paper mentions the Mauritius change in glowing terms without following up whether benefit or harm ensued, beyond the claimed 5-year drop in cholesterol.[7] Palm oil reduction was modelled for India in 2013, and a doubled palm oil tax has been implemented in Fiji since, all in papers citing the 1987-1992 Mauritius cholesterol drop.[8, 9]
But none follows that citation up with any hard outcomes.

 Conversely, none of the papers on health in Mauritius since 1992, charting worsening trends, and in which the Finns still feature as authors, mentions the oil change of 1987. However, the earlier paper had contained a warning:[2]

 "Whether the replacement of palm oil by soya bean oil, rich in n-6 polyunsaturated fatty acids, is the optimal dietary change may be questioned... the consumption of fats high in polyunsaturated fatty acids may lead to increased concentrations of free radicals and oxidised low-density lipoprotein, which may promote the progression of atherosclerosis. Therefore, notwithstanding the apparent success of the intervention in Mauritius, an oil high in monounsaturated fatty acids, such as olive oil or rapeseed oil, might be preferable if such an oil substitution were currently being planned."

 

It appears now that both saturated fat in the diet, and a low intake of omega 6 linoleic acid,  are beneficial in terms of the incorporation of the omega 3 fatty acids EPA and DHA into circulating lipids and cells.[10, 11, 12, 13] EPA in particular is anti-inflammatory, and is an approved drug for the prevention of CVD.[14]

 "These observations indicate that the efficacy of n-3 fatty acids in reducing arachidonic acid level is dependent on the linoleic acid to saturated fatty acid ratio of the diet consumed."[11]

 "The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids."[13]

 

The conversion of linoleic acid to arachidonic acid, and the peroxidation of arachidonic acid to aldehydes which interfere with insulin signaling, as well as its conversion to cannabinoids which increase adipocyte growth, in a context of decreased omega 3 availability from high LA and low SFA diet, are pathways that may explain the eventual adverse outcomes in Mauritius, especially in a population with high sugar availability.[15,16]

 "Our recent finding that sucrose and other high glycemic index carbohydrates abrogate the antiobesity effect of n-3 PUFAs might, at least in part, provide an explanation to the apparent discrepancy between human and rodent intervention studies, and the lack of effect in some human trials. In addition to the amount and type of carbohydrates, the levels of n-6 PUFAs, linoleic acid in particular, in the background diet might influence the antiobesogenic effect of n-3 PUFAs."[15]

 

It seems that, in the matter of diet, public health experts cannot be relied on to investigate the possibility that they have made a mistake. They control the narrative so that a (questionable) historical change in cholesterol within a 5-year period is considered evidence that a lifetime intervention is valuable, yet a nation-wide worsening of hard endpoints after that intervention can be ignored. Certainly the diabetes disaster in Mauritius can have had many causes, but the possibility that the soya bean oil intervention was one of them has not even registered in the medical literature over a 30 year period, let alone been tested.

 H/T Louise Stephen @LouiseStephen9 author of  'Eating Ourselves Sick' for bringing this intervention to my attention.

Postscript: it will be obvious to students of evidence-based medicine that the quality of evidence used to create this argument has left much to be desired. With the exception of the date and intent of the intervention and the diabetes incidence data, nothing here tells us quite what we want to know. For example, circulatory disease as a percentage of mortality is a suggestive but imperfect measure, even before the coding change. So there will be those who read this article and feel justified in dismissing the need for it.
But I ask them to look at things another way - the data in this page is, to the best of my knowledge, the sum total of the published, peer-reviewed evidence on the subject. The Mauritius intervention - a legal disruption of the saturated fat supply to replace it with unsaturated fat within an entire community, in a way designed to target its most vulnerable members - has been the masturbation fantasy of a certain type of public health epidemiologist for as long as I can remember. There is a constant supply of peer-reviewed publications modelling the long-term effect of such an intervention on the putatively preventable causes of mortality, and there have been none directly investigating the impact on those causes in this case - where the long-planned intervention actually happened.
The reasons for this neglect are a matter for conjecture; we may hear future tales of suppressed data and publication bias as we did with the Sydney Heart Study and Minnesota Coronary Experiment studies (both of which also involved changes of fat products given to a population, rather than the less certain changes of mere advice given in most other diet-heart studies)[17] but the conclusion ought surely to be that the modelling should stop until the facts have been checked. 

References

[1]  Dowse GK, Gareebo H, Alberti KGMM, Zimmet P, Tuomilehto J, Purran A, et al. Changes in population cholesterol concentrations and other cardiovascular risk factor levels after five years of the non­communicable disease intervention programme in Mauritius. BMJ 1995;311:1225­9.

 

[2]  Uusitalo U, Feskens EJM, Tuomilehto J, Dowse G, Haw U, Fareed D, et al. Fall in total cholesterol concentration over five years in association with changes in fatty acid composition of cooking oil in Mauritius: cross sectional survey. BMJ 1996;313:1044­6.

 

[3]  Chandrasekharan N, Sundram K. Fall in cholesterol after changes in composition of cooking oil in Mauritius. BMJ. 1997;314(7079):516. doi:10.1136/bmj.314.7079.516

 

[4]  Morrell, S., Taylor, R., Nand, D. et al. Changes in proportional mortality from diabetes and circulatory disease in Mauritius and Fiji: possible effects of coding and certification. BMC Public Health 19, 481 (2019) doi:10.1186/s12889-019-6748-7

 

[5]  Söderberg S, Zimmet P, Tuomilehto J, de Courten M, Dowse GK, Chitson P, Gareeboo H, Alberti KG, Shaw JE. Increasing prevalence of Type 2 diabetes mellitus in all ethnic groups in Mauritius. Diabet Med. 2005 Jan;22(1):61-8.

 

[6]  Magliano DJ, Söderberg S, Zimmet PZ, et al. Explaining the increase of diabetes prevalence and plasma glucose in Mauritius. Diabetes Care. 2012;35(1):87–91. doi:10.2337/dc11-0886

 

[7]  Mozaffarian D, Afshin A, Benowitz NL, et al. Population approaches to improve diet, physical activity, and smoking habits: a scientific statement from the American Heart Association. Circulation. 2012;126(12):1514–1563. doi:10.1161/CIR.0b013e318260a20b

 

[8]  Basu S, Babiarz KS, Ebrahim S, Vellakkal S, Stuckler D, Goldhaber-Fiebert JD. Palm oil taxes and cardiovascular disease mortality in India: economic-epidemiologic model. BMJ. 2013;347:f6048. Published 2013 Oct 22. doi:10.1136/bmj.f6048

 

[9]  Coriakula J, Moodie M, Waqa G, Latu C, Snowdon W, Bell C. The development and implementation of a new import duty on palm oil to reduce non-communicable disease in Fiji. Global Health. 2018;14(1):91. Published 2018 Aug 29. doi:10.1186/s12992-018-0407-0

 

[10]  Gibson, Robert A. Musings about the role dietary fats after 40 years of fatty acid research. Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 131, 1 – 5

 

[11] Garg ML, Thomson ABR, and Clandinin M T. Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism.

The Journal of Lipid Research, February 1990 , 31, 271-277.

 

[12] Dabadie H, Motta C, Peuchant E, LeRuyet P, Mendy F. Variations in daily intakes of myristic and alpha-linolenic acids in sn-2 position modify lipid profile and red blood cell membrane fluidity. Br J Nutr. 2006 Aug;96(2):283-9.

 

[13] Dias Cintia B, Wood LG, and Garg Manohar L. Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids. European Journal of Clinical Nutrition. 2016; 70: 812-818

 

[14] Budoff M, Brent Muhlestein J, Le VT, May HT, Roy S, Nelson JR. Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200-499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study. Clin Cardiol. 2018;41(1):13–19. doi:10.1002/clc.22856

 

[15] Madsen L, Kristiansen K. Of mice and men: Factors abrogating the antiobesity effect of omega-3 fatty acids. Adipocyte. 2012;1(3):173–176. doi:10.4161/adip.20689

 

[16] Clark TM, Jones JM, Hall AG, Tabner SA, Kmiec RL. Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users. Cannabis Cannabinoid Res. 2018;3(1):259-271. Published 2018 Dec 21. doi:10.1089/can.2018.0045


[17] Ramsden Christopher E, Zamora Daisy, Majchrzak-Hong Sharon, Faurot Keturah R, Broste Steven K, Frantz Robert P et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73) BMJ 2016; 353 :i1246
https://www.bmj.com/content/353/bmj.i1246

My Letter to Cochrane on the Hooper 2020 saturated fat meta

I submitted this on the Cochrane form at
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011737.pub2/comment

Others will have points to add about study quality and other factors, I have stuck to what I know (not wanting to waste my life battling an opponent who can obviously be reanimated an unlimited number of times).


The introduction to this meta-analysis includes an error uncorrected from the 2015 version.
Oliver 1953 measured total cholesterol, not LDL cholesterol. Further, it is relevant that every subject in Oliver 1953 had been eating the same hospital diet for at least 5 weeks before the cholesterol samples were taken, which does not support a diet-heart interpretation of the results.[1] (The presence of FH in the sample, and/or survivorship bias, are probably more reasonable interpretations)

[1] The Plasma Lipids in Coronary Artery Disease. Oliver MF, Boyd GS. Br Heart J. 1953 Oct;15(4):387-92. 

The section headed "Agreements and disagreements with other studies or reviews" has not addressed any written after 2014, meaning that this section has not been updated. There are several analyses of the diet heart trials since 2015 that should have been addressed (indeed, that should have been read before the current Cochrane review was designed). Some are listed below.[2,3.4]

[2] Hamley, S. The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials. Nutr J 16, 30 (2017). https://doi.org/10.1186/s12937-017-0254-5

[3] Thornley S, Schofield G, Zinn C, Henderson G. How reliable is the statistical evidence for limiting saturated fat intake? A fresh look at the influential Hooper meta-analysis. Intern Med J. 2019;49(11):1418‐1424. doi:10.1111/imj.14325

[4] Jeffery L Heileson, Dietary saturated fat and heart disease: a narrative review, Nutrition Reviews, Volume 78, Issue 6, June 2020, Pages 474–485, https://doi.org/10.1093/nutrit/nuz091

The discussion of Siri-Tarino 2010 in "Agreements and disagreements with other studies or reviews" claims that adjustment for lipids has confounded its null result, however Siri-Tarino at al had already addressed this by isolating studies not adjusted for lipids with no difference in their null result. This is quite understandable as adjusting for lipids also means adjusting for TG and HDL, cardiometabolic risk markers which can be beneficially infuenced by saturated fat and worsened by carbohydrate.
Studies which do not adjust for lipids can be favourable to saturated fat, for example the Malmo DCS, a high-quality observational study using a 7-day food diary and more rigorous exclusion criteria than is usual, or the 2019 dose-response meta-analysis of observational studies by Zhe et al.[5,6]

[5] Leosdottir M, Nilsson PM, Nilsson JA, Månsson H, Berglund G. Dietary fat intake and early mortality patterns--data from The Malmö Diet and Cancer Study. J Intern Med. 2005;258(2):153‐165. doi:10.1111/j.1365-2796.2005.01520.x

[6] Zhu, Y., Bo, Y. & Liu, Y. Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies. Lipids Health Dis 18, 91 (2019). https://doi.org/10.1186/s12944-019-1035-2

The claim that greater lowering of LDL in trials being associated with greater reduction of events supports the diet-heart hypothesis may be unsound. Persons in good metabolic health are at significantly lower risk of CVD events despite other risk factors.[7] Persons who are obese, have diabetes, or the metabolic syndrome do not usually experience drops in LDL cholesterol when fat in the diet is changed; the subjects in the feeding studies cited, who did experience such drops, were healthy volunteers.[8,9,10]

[7] Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Intern Med. 2001;161(3):361‐366. doi:10.1001/archinte.161.3.361

[8] Flock MR, Green MH, Kris-Etherton PM; Effects of Adiposity on Plasma Lipid Response to Reductions in Dietary Saturated Fatty Acids and Cholesterol, Advances in Nutrition. 2011;2,(3):261–274, https://doi.org/10.3945/an.111.000422

[9] Benatar JR, Sidhu K, Stewart RAH. Effects of High and Low Fat Dairy Food on Cardio-Metabolic Risk Factors: A Meta-Analysis of Randomized Studies. Tu Y-K, ed. PLoS ONE. 2013;8(10):e76480. doi:10.1371/journal.pone.0076480.

[10] Lefevre M, Champagne CM, Tulley RT,et al. Individual variability in cardiovascular disease risk factor responses to low-fat and low-saturated-fat diets in men: body mass index, adiposity, and insulin resistance predict changes in LDL cholesterol. Am J Clin Nutr. 2001;82(5):957–963, https://doi.org/10.1093/ajcn/82.5.957

It is also relevant that from 2004 the Swedish population began to reject diet-heart advice, to such an extent that butter sales rose and margarine sales dropped; cholesterol levels also rose.[11] Yet as recently as 2018 mortality from, and incidence of, AMI was continuing to decline in Sweden. In fact incidence of AMI had stayed stable from 1987 to 2005, after which it began to drop from 42,263 PA to 25,789 PA in 2018.[12]


[11] Johansson I, Nilsson LM, Stegmayr B, Boman K, Hallmans G, Winkvist A. Associations among 25-year trends in diet, cholesterol and BMI from 140,000 observations in men and women in Northern Sweden. Nutr J. 2012;11:40.

[12] Data accessed from Swedish Social Registry website 28/05/20 https://sdb.socialstyrelsen.se/if_hji/resultat.aspx

Uncoupling - Saturated fatty acids and glucose are preferred muscle fuels, but unsaturated fats act as buffers

An intriguing new study looked at 2 different types of enteral feeding in 60 critically ill patients for 7 days. The fat-based formula was 37%E glucose, so this was not a test of a low carb diet, and predictably the differences in glucose and insulin AUC, though trending in the right direction, were not significant.[1]

The significant finding was higher resting energy expenditure (REE) in the higher-fat group.

In my opinion this was not an effect of higher fat feeding but an effect of a high intake of a particular type of fat – no-one in the real world would ever eat 45% of energy as fat from rapeseed and sunflower oil exclusively (if nothing else, natural protein foods would supply other fats not found in the protein isolate used here).

“Fat-based EN formulas contain 45% fat, 37% carbohydrates, 18% protein, and 2.3 g of fiber per 100 ml, whereas glucose-based EN formulas are comprised of 30% fat, 55% carbohydrates, 15% protein, and contain 1.5 g of fiber per 100 ml. Both formulas have a caloric density of 1 kcal/ml and contain rape seed oil and sunflower oil. Initial assessment of resting energy expenditure (REE) was performed for each patient using the technique of indirect calorimetry. Target energy was 25% above the measured REE [13]. Both study groups received early EN that was initiated with the target dosage and continuously administered at a constant rate for 7 days via a nasogastric tube.”

The diet was very high in monounsaturated and polyunsaturated fat, and very low in saturated fat.

Unsaturated fats are well-known to activate uncoupling proteins in the mitochondria of muscle and adipose cells (in brown adipose tissue, there is good evidence that saturated fats can drive uncoupling; brown adipose is a highly functional cell type that exists for this sort of thing rather than storage, so I’m going to ignore it for now).[2,3]

I’m really interested in fuel use by muscle. The big, novel question in physiology today bar none is the lean mass hyper-responder lipid profile discovered by Dave Feldman (@DaveKeto). Because this relates to muscle mass/fat mass (and activity) ratio, and because different fatty acids in people eating normal diets have differential effects on lipid profiles, it’s necessary to know how muscles use fats before we investigate whether this can influence a lipid profile.

Effect of fatty acids on D-[U-14C]glucose oxidation in 1h incubated rat soleus (A) and extensor digitorium longus (EDL) (B) muscles. Muscles were incubated for 1 h in the absence or presence of 10 mU/mL insulin and/or 100 μM of different fatty acids.

Here’s a study on two types of muscle cell isolated from rats which shows a different effect of saturated vs unsaturated fats in extensor digitorium muscle (the soleus muscle, A, is less clear but I'm going with B for now; however the faster oxidising (medium chain) SFAs in A behave like palmitate in B).[4] To summarise the findings, unsaturated fats activate uncoupling; that is, a proportion of the potential energy released by their beta-oxidation is wasted, instead of generating ATP (the more double bonds, the more uncoupling). And this wastage – which will produce extra heat - allows the cell to burn extra glucose at the same time to make up the shortfall in ATP.

This is what is meant by unsaturated fats improving insulin sensitivity. Glucose and saturated fatty acids are the two preferred fuels of muscle cells, but they exist in competition. At times of energy excess, they would be at loggerheads if both were available together without other “softer” fuels. The effect of unsaturated (uncoupling) fats is to buffer the potentially harmful effect of this competition, by occupying the beta-oxidation mechanism (carnitine etc) yet leaving some ADP free for both glucose and SFA catabolism to convert to ATP. When glucose is restricted, the saturated fat level of the blood falls, despite a higher intake, because the competing effect of glucose and its insulin-driven uptake is removed. At this extreme, the buffering effect of unsaturated fat is unnecessary. At fat intakes below 37%, on the other hand, a differential effect on insulin sensitivity can more easily be detected, because glucose is the primary fuel, and insulin is driving SFA synthesis and retention.

(Thus the low fat diet, especially with refined carbs at current availability, was the very thing that painted us into the corner where there might be some reason to worry about the types of fat we use! Who the hell wants to be in that shithole.)

Strictly speaking we don’t need to consume unsaturated fats (beyond tiny EFA amounts of PUFA) because we can make oleic acid MUFA from SFA by DNL elongation and desaturation, although there is genetic variation in the ability to do this. Realistically speaking, this separation of SFA from MUFA in the diet is never going to happen anyway. Humans eat fat of all types, not SFA, MUFA or PUFA.

Although linoleic acid was an uncoupling fat in muscle in vitro, muscle in vivo may not be using much of this fuel. LA has a high rate of conversion to other lipids (cholesterol and SFA) in liver, is used to make eicosanoids and is otherwise peroxidizable, and is still stored in adipose in amounts that seem excessive in proportion to dietary intakes. In practical terms, oleic acid (C18:1) is probably always the dominant uncoupling fatty acid in muscle, and the more unsaturated fats (which would uncouple more) are lousy fuels. This might(?) help to explain the prevalence of CPT1A mutations, which suppress fatty acid oxidation on high fat diets, in populations with a high take of fat from oily fish (Inuit, Faroe Islands, Northern Japan).[5]

There’s another pathway by which UFA protects against SFA-glucose competition in muscle – in humans, triglyceride synthesis always requires at least one UFA.[6] So you can’t store any excess of SFA that turns up in a cell without some UFA; this is also a form of buffering that clears the track for whichever of the preferred fuels is dominant. Without it, incoming glucose would drive SFA elongation into excess ceramide, and the cell would be stuffed.

So in our critically ill population, an enteral diet very high in unsaturated fats produced a higher REE through uncoupling, and improved insulin sensitivity non-significantly (the control diet was relatively high in UFA by normal standards anyway). I’m not sure what the split of muscle vs adipose and other tissue fuel use would have been for bed-rest REE (I'm only using that study for a kicking-off point here). I’m told that elevated REE isn’t desirable in the critically ill. Maybe one day a more sensible enteral formula including, say, beef fat will be tested.

If you are overeating on a higher carb diet, the various energetically futile aspects of UFAs could be protective of your metabolism (but the eicosanoids and peroxidation products of PUFAs, especially LA, could well catch up with you eventually if you rely on those rather than MUFA). If you are restricting carbs, working hard, undereating or IF, or otherwise burning fat, do you really want to generate a lot of heat for less available energy? I can’t see a high degree of uncoupling being of benefit in endurance activities where heat loss is maxed out. I can’t see it being anything but exhausting. Even the Inuit may(?) have evolved to side-step it to some extent.
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references

[1] Wewalka M, Drolz A, Seeland B, et al. Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial. European Journal of Clinical Nutrition. 2018;72,496–503
doi:10.1038/s41430-018-0111-4

[2] Graier WF, Trenker M, Malli R. Mitochondrial Ca2+, the secret behind the function of uncoupling proteins 2 and 3? Cell calcium. 2008;44(1):36-50. doi:10.1016/j.ceca.2008.01.001.

[3] Romestaing C, Piquet M-A, Bedu E, et al. Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutrition & Metabolism. 2007;4:4. doi:10.1186/1743-7075-4-4. LINK

[4] Hirabaraa SM, Silveiraa LR, Alberic LC, et al. Acute effect of fatty acids on metabolism and mitochondrial coupling in skeletal muscle. Biochimica et Biophysica Acta (BBA) - Bioenergetics
Volume 1757, Issue 1, January 2006, Pages 57-66. LINK

[5] https://yk-health.org/images/3/36/Arctic-Variant-CPT-1.pdf

[6] Henique C, Mansouri A, Fumey G, et al. Increased Mitochondrial Fatty Acid Oxidation Is Sufficient to Protect Skeletal Muscle Cells from Palmitate-induced Apoptosis. J Biol Chem. 2010;
285, 36818-36827. LINK