The Science of Human Potential

Jim Mann’s new study: are high fat diets really dangerous, or is soybean oil toxic?

We were surprised to hear this Radio New Zealand interview with Jim Mann regarding a Chinese study he co-authored.[1] In it he predicts various terrible things for people eating LCHF diets, which we think is out of line and not supported by the study.

In fact, the LCHF and Paleo community have been warning about exactly the type of diet that was used in the study – high in energy from soybean oil, rice, and wheat – for years, and Jim Mann’s crowd have attacked us for that, while the NZ Ministry of Health and Heart Foundation they advise has actively promoted such a diet. So it’s ironic that, as soon as we’re proved right, this is presented as evidence against our own, quite different advice – rather than being acknowledged as the humbling result it is for those supporting the current guidelines.

Professor Jim Mann of Otago University Department of Human Nutrition and Medicine

“Of particular interest was what happened to the bacterial flora of the gut, the microbiome underwent radical changes in these three different groups.
The low fat group had a bacterial profile which was compatible with low risk of a number of western diseases: heart disease and cancer.
The high fat group had a very different profile of bacteria in their gut, one more compatible with an increased risk of bowel cancer and also a much higher risk of inflammation leading to cardiovascular disease, heart disease and possibly diabetes,” Prof Mann says.
The results, he says, were “pretty scary.”
“It’s a strong message for what is happening in China, but I believe also a strong message for New Zealand and other similar countries where at least some people believe there are benefits to a high fat diet.”
All three groups had consistent and similar intake of vegetables, he says.
“A lot of people have argued you can have a high fat diet as long as you have a lot of veggies, I think that’s a serious misapprehension. If you are having a really high fat diet you’re not going to get a high fibre diet at the level of fibre that will be protective against these diseases.”

So what was the study?

“In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18–35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated.”

The most important part of the paper is this statement:

Notably, the predicted lipopolysaccharide biosynthesis and arachidonic acid metabolism pathways were also increased in response to the higher-fat diet. Lipopolysaccharide is known to induce the release of arachidonic acid and its inflammation-involving metabolites, such as prostaglandins, thromboxane and leukotrienes. It should be noted that the intake of polyunsaturated fatty acids (PUFAs) was relatively high in the higher-fat diet group (24% of total energy) owing to exclusive use of soybean oil, which is rich in n-6 PUFA. A higher intake of n-6 PUFA has been reported to have proinflammatory effects.

In the interview, host Jesse Mulligan, who is a chef and knows his oils, does a great job of extracting this part of the story from Prof Mann. The n-6 (omega-6) PUFA in soy and other seed oils is linoleic acid; linoleic acid is the precursor of arachidonic acid (AA) and high levels drive AA synthesis. Lipopolysaccharide is also known as endotoxin and is a product of gram-negative bacteria that stimulates an immune response if it enters the bloodstream; a little endotoxin seems to be beneficial, but a lot can drive inflammatory diseases by activating the TLR4 receptor on immune cells.[2]

Now, the traditional Chinese diet varies across regions so that it is hard to generalise, but the low fat Southern version looks like this – lots of green and coloured vegetables ( a very wide diversity, not just a large quantity), nose-to-tail meat (mostly pork and chicken), eggs, legumes, and white rice. Though low in fat, it can be relatively high in cholesterol due to the use of organ meats. Cooking can be by steaming, or stir-frying using small amounts of various oils. The dietary transition has seen more deep-frying in oils and the use of more oils in processed foods. Most of this is soybean oil (the majority of the soy grown in the former Amazon rainforest is now exported to China where it is used to make oil and soy protein, some of which is no doubt exported to NZ and the Pacific).

The equivalent of a 40% seed oil diet in NZ would be deep fried meals from KFC, plus Best Foods mayonnaise – popular foods in the more deprived areas of NZ.

Now, why would a high fat diet be bad for the microbiome? A moment’s thought will show that this doesn’t make sense as a generalisation. The microbiome is established in infancy, starting with birth when bacteria are transferred from the mother. The diet in infancy for mammals is, by definition, milk, a food always high in saturated fat and low in polyunsaturated fat. At day 16, human breast milk is 54% fat; of this fat 44.6% is saturated, 37.6% is monounsaturated, 14.6% is polyunsaturated omega-6 and 3.1% is omega-3.[3] in hunter-gatherer populations without access to seed oils the omega-6 content is lower – e.g. 10% in the Tsimane of Bolivia vs 18% in the population of Cincinnati, USA.[4]

Breast milk contains small amounts of soluble fibre, and lactose which lactobacillus can ferment but which is mostly absorbed and used for energy and growth.
However – lactobacillus also metabolise saturated fats. And some lactobacillus species make saturated fats that many other bacteria rely on between meals – these are the odd-chain fatty acids, C15 and C17, which you’ll find in dairy, beef, and lamb fat, but other dietary saturated fats can substitute for C15 and C17 when their production is disrupted by alcohol.[5]

Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis* and reduces ethanol-induced liver injury in mice.
(*Eubiotics (Greek eu = good/healthy, bios = life) is the science of hygienic/healthy living. The term is used in the feed industry where it refers to a healthy balance of the microbiota in the gastrointestinal tract.)

And really, this should be obvious – if you buy yoghurt, the original probiotic food, you will find only two types to choose from – that made from milk (the animal food highest in saturated fat), and the vegan yoghurt made from coconut (the plant food highest in saturated fat).

Don’t blame the butter for what the soyabean did.

It has been known since 1945 that polyunsaturated fatty acids are toxic to lactobacillus and other gram-positive bacteria.[6] In the China trial, the high soybean diet decreased levels of the gram-positive bacteria, Faecalibacterium, and increased levels of the gram-negative bacteria Bacteroides and Alistipes.[1]  A 2018 review [7] stated that:

Linoleic acid and the other two major unsaturated FAs in SBO, oleic acid (18:1), and alpha-linolenic acid (18:3), are known to be bacteriostatic and/or bactericidal to small intestinal bacteria as non-esterified (free) fatty acids in vitro at concentrations found in the small intestine (). The primary modes of killing include permeabilization of cell membranes () and interference with FA metabolism (). Affected microbes are predominantly Gram-positive bacteria including the genus Lactobacillus (). Lactobacilli are particularly important as they are considered beneficial members of the human small intestine (). They have been shown to be growth inhibited by the specific FAs present in SBO (). It is interesting to note that the human-associated L. reuteri underwent a population bottleneck that coincides with the increase in SBO consumption in the U.S. and is far less prevalent than it was in the past ().  In the 1960’s and 1970’s prior to the emergence of SBO as a major dietary fat source, L. reuteri was recovered from the intestinal tract of 50% of subjects surveyed and was considered a dominant Lactobacillus species of the human gut (). Today, however, it is found in less than 10% of humans in the USA and Europe (), yet it is present at a reported 100% prevalence in rural Papua New Guineans ().

Yet the paper Jim Mann co-authored cites none of this research. There is only one reference in it (46) to the possibility that a high omega-6 intake can be inflammatory,  and this review does not mention the effect on the microbiome – despite being written by microbiologists.

This sort of thing is all-too common – a lack of curiosity in nutrition research. To plan an experiment like the Chinese soybean oil trial takes years. If you’re planning to feed an unusual amount of linoleic acid – 24% of energy – to people and measure its effects on the microbiome, why are you not curious enough to search for the evidence about the effect of linoleic acid on the microbiome? If you think more fat is bad fat, whatever its composition, you might miss this step. It’s possible that reference 46 and the comment about linoleic acid was added by a reviewer and was not even part of the paper as originally submitted. Or, it might have been included by Jim Mann, who is not a complete fool and who has long been exposed to Paleo arguments about omega-6, but went over the heads of his coauthors, the microbiologists.

So the microbiome results are no surprise to us (though predicting disease from the microbiome at our present stage of knowledge would be about as reliable as predicting it from tea leaves or tarot cards, gram-positive lactobacillus and bifidus probiotics have been well-tested and are for example associated with a reduction in rehospitalization for mania in bipolar disorder, HR 0.26, 95% confidence interval [CI] 0.10, .69; P = .007)[8].
But what is surprising, and should have surprised Jim Mann, is that LDL cholesterol did not go down on the high-PUFA diet. After all, the effect of PUFA on cholesterol has been the excuse for promoting these oils. There is increasing doubt about whether the effects of fat (amount or type) on LDL cholesterol counts has any important influence on CVD risk in the first place, but the news that soybean oil has no effect on LDL in a real world experiment means that there is no longer any rationale for recommending it.

 

So come on. This isn’t good interpretation of the results. The results of this high-soybean oil study say nothing about the effects of high fat diets when those fats are traditional fats that are not toxic to beneficial bacteria. The results of this study, where more energy came from carbs (mainly wheat and rice) than from fat, can say nothing about LCHF diets where wheat and rice are avoided or limited. Jim Mann’s comments about “the level of fibre that will be protective against these diseases” are based on epidemiology where very high levels of fibre are associated, not with IBD as in the real world, but with protection against all sorts of diseases. But we have news for him – very high levels of linoleic acid were also protective in epidemiology. Just not in the real world. The majority of associational results discovered in epidemiology are not borne out by later experiments, because associational epidemiology is inherently inaccurate, and can reflect the bias of epidemiologists, who are today also influencers of the populations they study.[9]

Postscript: The results of this study can help us to understand one of the more interesting nutritional epidemiology papers. The Malmo Diet and Cancer Study (MDCS) is a large cohort study that uses a 7-day food diary to collect data and also has stricter validation criteria than FFQ research, putting it into the highest category of evidence for such studies[10]. In the MDCS, of 8,139 male and 12,535 female participants (aged 44–73 y), there were 1,089 male and 687 female iCVD cases (Ischemic cardiovascular disease, including strokes and heart attacks) during a mean 13.5 year follow-up.  That’s about 1 in 8 men and 1 in 20 women. For iCVD, after full adjustment, fiber intake was negatively and significantly associated with iCVD in women (24 percent lower risk in the highest intake quintile compared to the lowest, 95 percent confidence interval −3 to −41 percent, p for trend = 0.022), but no other significant associations were noted, except a borderline (p=0.050) protective association of fibre with stroke for men. But here’s where it gets interesting – in the post-hoc analysis, adjusting for the other nutrients revealed that the combination of high fibre and high saturated fat was protective; that is, for men lowest quintiles of SFA and fibre combined had statistically significant HRs for iCVD of 1.82, which is pretty high, whereas high fibre/low SFA and high SFA/low fibre had the reference 1. For women, the lowest risk of iCVD, 0.36, was in the highest fibre, second highest SFA quintile, with the highest SFA highest-fibre quintiles being similar but non-significant.

Fibre and saturated fat associations with iCVD for men in Malmö

This result makes sense if both fibre and saturated fats are prebiotic foods, and if the combination supports eubiosis better than the combination of fibre and unsaturated fats.

References

[1] Wan Y, Wang F, Yuan J, et al Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Gut Published Online First: 19 February 2019. doi: 10.1136/gutjnl-2018-317609

[2] Marshall JC. Lipopolysaccharide: an endotoxin or an exogenous hormone? Clin Infect Dis. 2005 Nov 15;41 Suppl 7:S470-80.
https://academic.oup.com/cid/article/41/Supplement_7/S470/666706

[3] Jensen RG. Lipids in human milk. Lipids 1999 Dec;34(12):1243–71. http://pmid.us/10652985

[4] Martin MA, Lassek WD, Gaulin SJ, et al. Fatty acid composition in the mature milk of Bolivian forager-horticulturalists: controlled comparisons with a US sample. Matern Child Nutr. 2012;8(3):404-18.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851016/

[5] Chen P, Torralba M, Tan J, et al. Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice. Gastroenterology. 2014;148(1):203-214.e16.

[6] Kodicek E. The effect of unsaturated fatty acids on Lactobacillus helveticus and other Gram-positive micro-organisms. Biochem J. 1945;39(1):78-85.

[7] Di Rienzi SC, Jacobson J, Kennedy EA, et al. Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil fatty acids. Elife. 2018;7:e32581. Published 2018 Mar 27. doi:10.7554/eLife.32581

[8] Dickerson F, Adamos M, Katsafanas E. Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: A randomized controlled trial.
Bipolar Disord. 2018 Nov;20(7):614-621. doi: 10.1111/bdi.12652. Epub 2018 Apr 25.

[9] Ioannidis JPA. The Challenge of Reforming Nutritional Epidemiologic Research. JAMA. 2018;320(10):969–970. doi:10.1001/jama.2018.11025

[10] Wallström P, Sonestedt E, Hlebowicz J, et al. Dietary fiber and saturated fat intake associations with cardiovascular disease differ by sex in the Malmö Diet and Cancer Cohort: a prospective study. PLoS One. 2012;7(2):e31637.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031637