By George Henderson and Grant Schofield
Topics covered here
- Metabolic health and COVID-19 risk
- Possible roles of HDL in lung disease
- The microbiome and viral resistance
- Selenium and COVID-19
- Vitamins D and K2, and COVID-19
Bottom line for all of this:
Eating whole unprocessed food, especially that low in sugar, refined and processed carbohydrates, is likely to have benefits for your immune system and viral resistance generally.
If you are pre-diabetic, diabetic, overweight, or insulin resistant then this effect may be even more important.
COVID-19 numbers are falling sharply in NZ and we are on course to “eliminate” the virus, or probably more accurately restrict it so it’s easily managed. Vaccines are being trialed around the world already; but there are significant barriers to making a safe and effective vaccine for this disease, so we are not holding our breath. You certainly wouldn’t bet the country on a timely, safe, and highly effective vaccine.
There are also encouraging signs that some anti-viral drug combinations developed for hepatitis C treatment may be effective enough against COVID-19 (they need to be highly specific against HCV, but because COVID-19 is not usually a persistent virus, a drug that reduces the viral load by a log factor or two will probably be good enough, the immune system can do the rest).
Both these approaches take time (and money) and it may be years before a vaccine can reach everyone. And even then, it is unlikely to give the lasting herd immunity that some vaccines do. We have flu vaccines, but flu still goes round, and this is only partly due to unpredicted strains appearing that weren’t in the vaccine – when healthy elderly people have a flu vaccine, the rates of seroconversion or seroprotection (two different ways of measuring whether there are enough antibodies to prevent infection) are low, and the immunity doesn’t last as long. Immunologists worry that the same might be true of COVID-19 – not everyone infected has seroprotection going forward.
Metabolic disease and COVID-19 risk.
It is beyond obvious that metabolic disease greatly increases the risk of death in people who become infected with COVID-19.
New research from Glytec, the main supplier of diabetes software in the US, suggests that in-hospital mortality is more than quadrupled in COVID-19 patients with diabetes and hyperglycemia.
“People with diabetes who have not yet been infected with the SARS-CoV-2 virus [which causes COVID-19] should intensify their metabolic control as needed as means of primary prevention of COVID-19 disease,” according to expert panel guidance in the Lancet Diabetes & Endocrinology.
Diabetes and hyperglycaemia, as well as the metabolic syndrome and most cases of hypertension, can have their control greatly improved by carbohydrate restriction, calorie restriction, and/or fasting. The fewer carbohydrates are eaten, the fewer drugs are required to maintain glycemic control, and the more reliable (or “intense”) it is, because the usual, unavoidable errors in estimating diet and dose have less impact when numbers (of carbs, of drug units) are in a lower range. None of this is new or controversial knowledge, the main thing that is required from the practitioner is the ability to ignore the low-quality evidence from epidemiology (saturated fat, whole grains, low carbohydrate “diet score”) that is used by some people to confuse the issue. This evidence, such as it is, has zero to do with the utility of carbohydrate restriction for the control of metabolic disease. (But saturated fat and whole grains will get their time in court when we discuss immunity).
While there has been some focus on obesity and much on type 2 diabetes and the metabolic syndrome in the literature, an emerging risk factor seems to be HDL cholesterol which has causal links to respiratory fitness.
In this pre-print study of cases in 3 hospitals
Fasting hypoglycaemia was found in 21.4% of patients in mild 1 (14-day recovery) group with no case of fasting hyperglycaemia. In the mild 2 (30 day recovery) group, 34.1% of the patients had fasting hypoglycaemia, and 2.3% had fasting hyperglycaemia. Compared with mild COVID-19 patients, we found that 24% of severe COVID-19 patients had fasting hyperglycaemia and 4% had fasting hypoglycaemia.
Patients in the severe group had a lower level of serum total protein (59[58–63] vs. 65[63–70]), serum albumin (36[34–39] vs. 41[37–43]), total cholesterol (3.6[3.3–4.0] vs. 3.8[3.5–4.4]), and HDL-C (0.88[0.81–1.10] vs. 1.05[0.93–1.50]) compared with the mild 1 group (Table 2).
The difference in HDL cholesterol is more significant than that in total cholesterol, and is more likely to be causal. Why? Because HDL cholesterol is a marker of respiratory fitness, and ApoA1 is causal in lung health; it is involved in both the antioxidant protection of lung cells, and the lung’s immune function, which relies on “reverse cholesterol transport”-type movement of cholesterol.
Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol eﬄux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders.
HDL also protects populations of anti-inflammatory regulatory T-cells, T-Reg.
HDL could be worth looking at further in lung disease
To sketch in the possibility of this, we’re going to explore this American paradox – when the 397 residents of a Boston homeless shelter were tested for COVID-19, 146 people tested positive. As we might expect when 397 people are living together with little opportunity for distancing. However they reported the same low rate of cold and flu symptoms as the people testing negative.
Cough (7.5%), shortness of breath (1.4%), and fever (0.7%) were all uncommon among COVID-positive individuals.
This is another preprint, so results may change, but we wanted to see if we could explain this: what are the metabolic features associated with homelessness, if any?
We found a study of a homeless population in Estonia. N=51, 90% men. Is this is a suitable proxy for a US population? The result is striking enough that it may well be. These people had a wide range of metabolic variation across lipid, glycemic and inflammatory markers, but not one of them had HDL of <1 mmol/L or below the normal range (which has no upper limit). Usually, around 40% of a population will have low HDL. ApoA1 was normal or high, no-one was low.
More than half of the investigated patients had values of measured markers (hsCRP, TChol, LDL-Chol, TG, HbA1c, ApoA1, ApoB, Lp(a), Gluc) within normal range. Surprisingly, 100% of subjects had HDL-Chol within endemic norm.
In this peripatetic population, it is likely that a high activity level contributes to the HDL level. Of course our juxtaposition of these two studies proves nothing, and there are many reasons why homeless populations might be at higher risk after all, but it is an interesting finding. At any rate, COVID-19 is not picking off the highly fit, and the effect of HDL and ApoA1 on lung function helps explain this.
Besides physical activity, a low carb diet (which also improves VO2max) also raises HDL levels. As do saturated fats of the dairy and coconut type, which may have other benefits, as we will see in the next section. Saturated fat foods tend to raise LDL cholesterol, so is LDL cholesterol also relevant? This review suggests it is.
It is now increasingly recognized that lipids and lipoproteins play an important role in host defense as part of the innate immune system. For example, lipoproteins including HDL, chylomicrons, VLDL, and LDL can bind and neutralize LPS, lipoteichoic acid, and viruses.
Numerous studies have shown that animals that have elevations in serum lipid/lipoprotein levels are protected from the toxicity of LPS, whereas animals with low circulating lipid/lipoprotein levels are more sensitive to the toxic effects of LPS. Studies have shown that HDL may inhibit the ability of certain viruses to penetrate cells.
In other words, this is not a time to worry about the effect of your diet on cholesterol, if that diet helps you reach other goals.
Immunity and the microbiome.
As we mentioned earlier, flu vaccine responses in health elderly people are pretty disappointing, and this has been our major effort to reduce infections that cause pneumonia deaths in this population. The Cochrane review points out that RCT evidence is slim.
These results indicate that 30 people would need to be vaccinated to prevent one person experiencing influenza, and 42 would need to be vaccinated to prevent one person having an influenza-like illness.
Given how common influenza-like illnesses are, this, though better than no protection, is not the coverage expected from a really effective vaccine.
When we looked into the evidence for various supplements “boosting immunity”, some of the best evidence was for probiotics boosting vaccine responses, especially for flu vaccines in the elderly.
This research allows us to look closer at the data – probiotics and prebiotics double the rates of seroconversion and seroprotection (2 similar measures of immunity) in adults after vaccination for common flu strains. The effect is even stronger if the trails are restricted to only those looking at healthy elderly people (those not in hospital). There is a dose-response effect from longer duration of exposure to probiotics before vaccination.
Now, if you can double or triple antiviral immunity after a vaccine by giving a probiotic, then rates of immunity without the probiotic have to be pretty low. And if you dig down into these studies, they are around 30%. If you can double (or triple) that rate you’d have herd immunity.
The prebiotic studies are not that great, there are fewer of them, and the one that involved feeding isolated bean fibre to elderly people sounds unnecessarily harsh, but they do demonstrate the principle that just as you are what you eat, so are your microbes. As far as we can tell, there are two types of food that put the microbiome out of balance – one is refined carbohydrates (sugar and flour), which are missing the fibres that the better microbes like. So if you do eat grains, because you have no metabolic reason not to, be sure to eat whole grains, and if you do eat sugar, try to keep it in the fruit as much as possible. (but remember that gluten does weaken tight junctions in the gut, which may be undesirable for reasons that will appear later)
The other thing that good microbes don’t like a lot of is unsaturated fat. The beneficial gram positive bacteria that keep the gut in shape metabolise saturated fats – these are prebiotic. They have a limited capacity to tolerate unsaturated and especially polyunsaturated fatty acids. This may be why the “good shepherd” bacteria lactobacillus reuterii is declining in the US population, where it used to be very common. If you make a full-fat yoghurt, you need to use either dairy, or coconut, and these are the animal food and the plant food highest in saturated fat. There are yoghurts made with soy milk, but this is low in fat (1.61 g/L). The bacteria are fermenting sugars in the milk (and are able to make their own saturated fats) and to make a higher-fat yoghurt with soy it would probably be necessary to hydrogenate the soy oil.
After the NZ level 3 lockdown rush to buy fast food, there were probably a few people nursing a gut-ache. Refined carbohydrates and deep-fried seed oils can cause changes in the microbiome by killing off desirable species and boosting the population of more inflammatory ones. This is probably not great for immunity in the context of the ageing immune system.
COVID-19 sometimes appears as a gut infection, with symptoms of gastrointestinal distress and diarrhoea. Evidence from the US is that mild cases of COVID-19 have a longer course if gut symptoms appear first (30 days vs 14 days). Evidence from China is that gut symptoms early in the course of the disease predict more severe lung pathology.
Why would this be the case? If COVID-19 strongly infects the gut, it may interact with gut bacteria. This has been observed with polio, where specific bacteria enhance infection. The risk is that as viral infection of the lung proceeds, it will then be accompanied by LPS and other PAMPS from gut bacteria, and it is possible that signals from some bacteria are more inflammatory and predispose more to autoimmunity and sepsis than signals from, for example, lactobacillus species.
Of course it goes without saying that age and the comorbidities associated with poor COVID-19 prognosis will be associated with GERD, IBS, SIBO and the other clinical signs of dysbiosis. Anticholinergics (used to treat IBS) and PPI’s (used to treat GERD) are both associated with an increased risk of pneumonia.
How relevant this is is unclear, but it seems unlikely to be irrelevant.
Selenium and COVID-19 cure rates.
In our original factsheet we highlighted the likely role of selenium in viral outbreaks. Selenium is critical to immune cell function, especially in T-cells and macrophages where it provides an antioxidant defence against the ROS these cells generate, and also has critical functions in endothelial cells. Many RNA viruses, including HIV, HCV, ebola, and flu and coronaviruses, encode for large numbers of selenocysteine residues. This means that they have a high demand for selenium, and that infection can cause selenium deficiency if levels are low (the virus is sequestering selenium, which is unavailable to the body and lost when virus particles shed). Selenium helps the viral genome stay stable, and it is more likely to mutate in a selenium-deficient host, so it’s actually in our interests to give a virus like COVID-19 all the selenium it needs – getting enough selenium for both virus and host is a win-win situation.
A new study from China correlates COVID-19 cure rates with soil selenium status. While this is not individual-level data, the correlations are both large and highly specific and are unlikely to be due to different diagnostics or other random variations between regions.
Examining data from provinces and municipalities with more than 200 cases and cities with more than 40 cases, researchers found that areas with high levels of selenium were more likely to recover from the virus. For example, in the city of Enshi in Hubei Province, which has the highest selenium intake in China, the cure rate (percentage of COVID-19 patients declared ‘cured’) was almost three-times higher than the average for all the other cities in Hubei Province. By contrast, in Heilongjiang Province, where selenium intake is among the lowest in the world, the death rate from COVID-19 was almost five-times as high as the average of all the other provinces outside of Hubei.
Most convincingly, the researchers found that the COVID-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair, in 17 cities outside of Hubei.
New Zealand soil is relatively low in selenium; we recommend, at least for the duration of the pandemic, eating either 2-3 Brazil nuts per day or supplementing 50-100mcg selenium. Clinicians brand sodium selenite drops provides a cheap option with lower toxicity than other supplement forms, but many multivitamins made for the NZ market supply useful amounts of selenium. Selenium from supplements should not exceed 200mcg per day.
Vitamin D and vitamin K2
Vitamin D status is also highly correlated (at an individual level) with the risk of dying from COVID-19 in Indonesia. It may be that some of the low vitamin D is due to an effect of infection, but this does not completely explain the protective effect of higher levels, which is consistent with animal experiments in lung disease models. We were lucky in NZ and Australia that COVID-19 hit at the end of summer, when vitamin D levels are highest, but many people will need to supplement in winter to maintain adequate levels.
Vitamin K status has also correlated with survival from COVID-19, but again this may be in part an effect of infection (vitamin K levels were not tested – a marker of calcium transfer was used, which shows the function of vitamin K2 in the body, and is known to decline in kidney disease). Vitamin D3 with vitamin K2 supplements are available – from Clinicians again – no they don’t pay us, they just have a good evidence-based policy when it comes to formulating supplements! Vitamin K1 is found in green leafy plants, vitamin K2 (a small amount of which is made from K1 in the body) is sourced from some fatty animal foods, and some fermented animal and plant foods. The best dietary sources of D3 are salmon, eggs, and fatty pork.
 Nie, Shuke & Zhao, Xueqing & Zhao, Kang & Zhang, Zhaohui & Zhang, Zhentao & Zhang, Zhan. (2020). Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study. 10.1101/2020.03.24.20042283.
 Gordon EM, Figueroa DM, Barochia AV, Yao X, Levine SJ. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease. Front Pharmacol. 2016;7:323. Published 2016 Sep 21. doi:10.3389/fphar.2016.00323
 Rueda CM, Rodríguez-Perea AL, Moreno-Fernandez M, et al. High density lipoproteins selectively promote the survival of human regulatory T cells. J Lipid Res. 2017;58(8):1514–1523. doi:10.1194/jlr.M072835
 COVID-19 outbreak at a large homeless shelter in Boston: Implications for universal testing. Travis P. Baggett, Harrison Keyes, Nora Sporn, Jessie M. Gaeta. medRxiv 2020.04.12.20059618; doi: https://doi.org/10.1101/2020.04.12.20059618
 Kaldmäe M, Zilmer M, Viigimaa M, et al. Cardiovascular disease risk factors in homeless people. Ups J Med Sci. 2011;116(3):200‐207. doi:10.3109/03009734.2011.586737
 Feingold KR, Grunfeld C. Lipids: a key player in the battle between the host and microorganisms. J Lipid Res. 2012;53(12):2487‐2489. doi:10.1194/jlr.E033407
 Demicheli V, Jefferson T, Di Pietrantonj C, Ferroni E, Thorning S, Thomas RE, Rivetti A. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2018, Issue 2. Art. No.: CD004876. DOI: 10.1002/14651858.CD004876.pub4.
 Lei WT, Shih PC, Liu SJ, Lin CY, Yeh TL. Effect of Probiotics and Prebiotics on Immune Response to Influenza Vaccination in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2017;9(11):1175. Published 2017 Oct 27. doi:10.3390/nu9111175
Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes [published online ahead of print, 2020 Apr 15]. Am J Gastroenterol. 2020;10.14309/ajg.0000000000000664. doi:10.14309/ajg.0000000000000664
 Jinsong Zhang, Ethan Will Taylor, Kate Bennett, Ramy Saad, Margaret P Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, , nqaa095, https://doi.org/10.1093/ajcn/nqaa095
 Thomson CD, Chisholm A, McLachlan SK, Campbell JM. Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr. 2008;87(2):379‐384. doi:10.1093/ajcn/87.2.379
 Raharusun, Prabowo and Priambada, Sadiah and Budiarti, Cahni and Agung, Erdie and Budi, Cipta, Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study (April 26, 2020). Available at SSRN: https://ssrn.com/abstract=3585561
 Dofferhoff, A.S.; Piscaer, I.; Schurgers, L.J.; Walk, J.; van den Ouweland, J.M.; Hackeng, T.M.; Lux, P.; Maassen, C.; Karssemeijer, E.G.; Wouters, E.F.; Janssen, R. Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19. Preprints 2020, 2020040457 (doi: 10.20944/preprints202004.0457.v1).
Nutrition guidelines for dental care vs. the evidence: Is there a disconnect?
Dental caries is the most common chronic childhood disease in New Zealand. The most recent data from the Ministry of Health (MOH) showed that 38% of five-year old children were diagnosed with dental caries in 2017, with a higher prevalence observed among Māori and Pacific children compared to children of other ethnicities. Some 7700 children aged five years old and under require extraction of decayed teeth under general anaesthesia; in addition, the cost of this operation for New Zealand taxpayers is some NZD $132,000 per working day. Concurrently, obesity and related chronic diseases including diabetes, cardiovascular disease and neurological disease are the most challenging public health problems. New Zealand is experiencing an obesity epidemic; New Zealanders are the third most overweight and obese population among countries included in the OECD. Approximately 67% of all New Zealanders over 15 years of age are overweight and the prevalence of obesity is 27%.
There is considerable evidence that a common dietary behaviour – high frequency consumption of ultra-processed, high carbohydrate foods – is the principal causal factor for both dental caries, and presentation of children and young people as overweight or obese. The relationship between high dietary intakes of sugar and dental caries is well established. In addition, high, and frequent consumption of processed foods containing sugars and starches are implicated in dental caries, and presentation of children and young people as overweight or obese.
Conversely, consumption of full-fat dairy products by children and young people is associated with reduced risks dental caries, body fatness, and hypertension. In addition, dairy product intake was associated with enhanced lipid profiles benefits for bone mineralisation. Recent systematic reviews found that intake of milk and other dairy products are consistently found to be either not associated, or inversely associated, with obesity and anthropometric indicators of adiposity in children,
Although government-endorsed dietary guidelines for young people correctly provide recommendations to decrease intake of high-sugar foods, recommendations are also provided to increase the amount, and frequency of consumption of high carbohydrate foods as children age.
This means that promoted foods include ultra-processed items that are associated with dental caries and other chronic disease.[5-9] Further, included in the MOH food suggestions are refined carbohydrates (such as cornflakes) and foods listed in the highest NOVA category of ultra-processed foods, such as plain sweet biscuits and tortillas. This advice for children contradicts evidence of the dietary causes of dental caries and contradicts the nutritional, metabolic and hormonal theory of metabolic health as the cause of obesity. Consumption of breads, cereals and other ultra-processed refined sugar-and starch-containing foods is associated with dental caries, is implicated in insulin resistance, and is associated with obesity in older children and adolescents.
Additional advice is provided in the dietary guidelines to choose low-fat options when consuming dairy produce. Although the anti-cariogenic properties of milk products are acknowledged in the guidelines, recommendations about dairy intake promote low-fat dairy products, in direct opposition to epidemiological evidence. Full-fat dairy products have not been associated with obesity in child and adolescent populations, and studies indicate that whole milk consumption is associated with favourable effects on body composition and lipid profiles of children. This advice directly contradicts evidence of the dietary causes of both dental caries and obesity and does not reflect the evidence regarding observed associations between the consumption of full-fat dairy produce and reduced dental caries, obesity and other indicators of health. Examples of the advice is provided in Table 1 below.
Table 1. Specific food and nutrition guidelines for healthy eating in children and young people pertaining to dietary factors and evidence for prevention of obesity and dental caries in young people.
|Dietary factor||Weight management||Optimal oral health|
|Carbohydrate intake||“Eat a variety of foods from each of the four major food groups each day…”
· … breads and cereals, increasing wholegrain products as children increase in age.
|“Eat a combination of foods at each meal, including whole grains…”
“Good oral hygiene and minimising intake of cariogenic foods and drinks are key behaviours in preventing dental caries”
|Recommendations for the “breads and cereals“ food group|
|Specific foods included||Recommendation (per day)||Serving size examples|
|All breads, cereals, rice and pasta (increasing wholegrain options as children age)||Pre-schoolers: at least 4 servings
Children: at least 5 servings
Young people: at least 6 servings
|1 medium slice of bread (26 g)
1 roll (50 g)
1 pita pocket or tortilla (50–80 g)
2 breakfast wheat biscuits (34 g)
½ cup muesli (55 g) ½ cup porridge (130g)
1 cup cornflakes (30 g)
1 cup cooked pasta or rice (150 g)
4 grainy crackers (40 g)
2 plain sweet biscuits (14 g)
1 cup plain popcorn
|Fat intake||Weight management||Optimal oral health|
|“Eat a variety of foods from each of the four major food groups each day…
· milk and milk products or suitable alternatives, preferably reduced or low-fat options
“Reduced or low- fat milk and milk products are the best choices because these foods include less saturated fat, and often more protein and calcium than high-fat alternatives.”
|“Eat a combination of foods at each meal, including whole grains, vegetables and fruit.”
“Anti-cariogenic foods and drinks are those that promote tooth remineralisation. They include foods high in calcium, phosphate and protein, such as milk and milk products”
|Recommendations for the “milk and milk products“ food group|
|Specific foods included||Recommendation (per day)||Serving size examples|
|Milk (includes calcium-fortified milk alternatives), cheese and yoghurt (choose low-fat options)||Pre-schoolers and children: at least 2–3 servings
Young people: at least 3 servings
|Glass of milk or calcium-fortified milk alternative (250 ml), one pot of yoghurt (150 g) 2 slices of cheese (40g)|
Given that the epidemics of dental caries the most common chronic disease of and metabolic disease are significant ongoing public health challenges in New Zealand and share common dietary causes, guidelines for healthy eating should focus on prevention of chronic disease through the lifespan by limit refined sugar-and starch-containing foods and encourage intake of whole foods, full-fat dairy items.
- Ministry of Health, Annual update of key results 2017/18 New Zealand Health Survey. 2019, Ministry of Health: Wellington.
- Beaglehole, R., Sugar sweetened beverages, obesity, diabetes and oral health: a preventable crisis. Pac Health Dialog, 2014. 20(1): p. 39-42.
- Dror, D.K. and L.H. Allen, Dairy product intake in children and adolescents in developed countries: trends, nutritional contribution, and a review of association with health outcomes. Nutr Rev, 2014. 72(2): p. 68-81.
- Dougkas, A., et al., A critical review of the role of milk and other dairy products in the development of obesity in children and adolescents. Nutr Res Rev, 2019. 32(1): p. 106-127.
- Monteiro, C.A., et al., Ultra-processed foods: what they are and how to identify them. Public Health Nutr, 2019. 22(5): p. 936-941.
- Campain, A.C., et al., Sugar-starch combinations in food and the relationship to dental caries in low-risk adolescents. Eur J Oral Sci, 2003. 111(4): p. 316-25.
- Fiolet, T., et al., Consumption of ultra-processed foods and cancer risk: results from NutriNet-Sante prospective cohort. Bmj, 2018. 360: p. k322.
- Srour, B., et al., Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Sante Prospective Cohort. JAMA Intern Med, 2019.
- Srour, B., et al., Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Sante). Bmj, 2019. 365: p. l1451.
- Weiss, R., A.A. Bremer, and R.H. Lustig, What is metabolic syndrome, and why are children getting it? Ann N Y Acad Sci, 2013. 1281: p. 123-40.
- Hayden, C., et al., Obesity and dental caries in children: a systematic review and meta-analysis. Community Dent Oral Epidemiol, 2013. 41(4): p. 289-308.
Some fun media with me….A public health professor believes New Zealand schools should run lunch programmes to reduce the consumption of processed and packaged food.
Listen to the interview (4 min and fun – tight here): Schools encouraged to run lunch programmes to promote healthy eating
Dr Richard Babor, a cancer surgeon, and his new TV show “How not to get cancer” attracted loads of attention. There was some negative reaction because people felt they were being unfairly blamed for getting cancer, because poor lifestyle was pinned as a major cause of cancer. I doubt that was the intention of the show. In fact, Dr Babor clearly started in the intro that “it’s no one’s fault personally” and this is an important point.
But it is a big public health issue. No one wants cancer, and we want to know if we can prevent it.
The way public health researchers have assessed the situation is to look at cohorts who behave in certain ways and those who do things differently. What we have seen is that things like smoking, poor diet, low fitness and activity, poor sleep and other lifestyle factors account for quite big differences. Maybe half of all cancers could be prevented by healthy lifestyle.
That’s not a personal fault of anyone. But it is a big societal issue. I’m assuming we all want along and healthy life.
We’ve grabbed smoking by the horns over the last few decades. Drinking is improving in some groups. Food guidelines and the food environment have been hijacked by the processed food industry. Fitness continues to plummet, especially in our kids.
This post is about fitness.
It’s about how some of the finer details which can make a big difference.
It includes the extra information that didn’t fit into the few minutes of my appearance on Dr Babor’s show. I’ve been asked a lot to write about this and provide some detail and “how to” of what he did and how he massively helped his fitness by slowing down, doing a little less (but still plenty) and boosting the physiology of the anti-cancer environment.
It’s about the finer details that are important for our long-term health and happiness. I’m assign there are a lot of people who want the best actable information about lifestyle and health, not the “minimum guidelines for couch potatoes”.
Fitness is medicine. So here goes….
The features of the pro- and anti-cancer internal environment
One way of thinking about human physiology around growth and repair cycles is to understand the catabolic versus anabolic states. In catabolism your body is repairing and tidying up what it has – it’s a non-growth, use-what-you-have state. In anabolism, you are growing more – cells divide – you grow, you store.
One view is that most modern humans end up spending far too much time in the anabolic (growth and storage) state, and not much time in the catabolic (repair and use) state. Because the anabolic state is one of inflammation – that’s what stimulates the process, then this chronic inflammation is never stopped and this is the root cause of modern chronic disease – cancer, heart disease and stroke, Alzheimer’s disease and dementia, and diabetes.
One way the catabolic environment might deal with early cancer cells is that they (early cancer cells) are metabolically disadvantaged in this state. Cancer cells themselves are unable to become catabolic. Early cancer and pre-cancer cells may be more likely to be recycled through autophagnic and apoptotic processes. The anabolic state is pro-cancer because it is a growth-promoting environment – exactly what early cancer cells want. The inflammation and reactive oxygen species might create further mutations to more aggressive cancer type cells.
There’s some speculation above, but I think the evidence points the fact that we could do with getting into the catabolic state from time to time. Regularly even.
The features of a catabolic state (cell repair, use of whats left, stimulated by nutrient stress)
- Low insulin and glucose
- Low IGF-1 (insulin-like growth factor)
- Low reactive oxygen species
- Ketogenic signalling
- High immune functioning
The features of an anabolic state (cell growth, storage, stimulated by food and stress)
- High reactive oxygen species
- High IGF-1
To be clear both states are essential for fully functioning healthy humans. But you do need to be able to access both.
What we need to get catabolic signalling going is nutrient stress. That is, not enough nutrients. This forces the body to stop the growth and scavenge through a process called autophagy (literally self eating) where every cell in the body uses the lysosome to recycle and find old organelles and scraps floating around inter- and even extra-cellularly.
It’s a process essential for optimal function, including probably the early destruction of cancer and pre-cancerous cells (see above).
Fasting (i.e. not eating) is the most obvious way of stimulating catabolism. Getting insulin higher (eating carbohydrate and protein) is the path to anabolism.
Fasting and fasting mimicking
Here are the known ways to get that catabolic environment. It turns out you can get the same (or similar) effects to fasting while still eating as well!
- Extended fasting. That’s right – not eating for a few days gets you right there. I’ve done this several times and you feel great. But it does have some drawbacks…Pros: Save money, get ketogenic signalling going quickly. Cons: You are not eating, people classify you as “that person”, and you may lose muscle mass and reduce your metabolic rate.
- Intermittent fasting. Not eating for longish periods during a day e.g. miss breakfast and lunch. I’ve done lots of this and wrote a book (What the Fast?) all about this. I find it a practical way to cycle in handout of the catabolic state. Pros: Pretty simple, save money, you have more time during the day to do other things. Cons: Still requires will power.
- A fasting mimicking diet (keto). I written even more about this in all the What the Fat? books. I like low carb as a base for living. Pros: It’s yummy, you feel full, you get the nutrients you need. Cons: It can be costly, takes preparation, and sometimes you feel a little limited in the pathological food world we live in.
- Fasting mimicking Exercise (FME). I’ve written almost nothing about this and it’s about time I did, because exercise training on a healthy diet where the intensity is low (at or below aerobic threshold) has a profoundly useful signalling effect on the body – it stimulates low glucose, insulin, IGF-1, increased ketones, and all the rest of the catabolic pathway. That’s why I’m calling it FME. Pros: It’s free, it’s fun, it’s super easy (the effort level is ridiculously and counterintuitively low), and you get the benefits like increased cardiorespiratory fitness (see below), relief of arthritis and back pain, better mood and mental health, and increase muscle mass and your metabolic rate. Cons: You have to do it, but even when you don’t feel like doing it, you return feeling like it was worth it.
So there is your quiver of catabolic tools. Most of you would have heard of the first three. Here’s to adding the fourth, FME!
Oh, but wait there’s more. Being fit is good for you for lots of reasons. Here’s some epidemiology.
Why fitness is medicine
It’s long been known that high fitness is associated with better health – living longer and with less disability. But there has always been a thought in public health that we may as well just tell the half of us who hardly move at all (or don’t meet the minimum physical activity guidelines) that any movement is good movement, and that 30 min of anything 5 days a week is enough.
True, it’s enough for the minimum benefit. You are way better off doing something than nothing. So if that’s you, read no further and go outside and get started.
There has also been a school of thought that we have people in society who take their fitness way too seriously. We even give them names like “fitness freak”. (I’ve been called that…)
I submit to you that there are many in society who want to have the full information about what constitutes optimal health and best possible outcomes. This is what this post is about in regards to fitness.
I guess the idea that you can wreak havoc by overdoing it is real. I have over-trained, and achieved less than optimal fitness by being an idiot about it. Hopefully I can show you the best way to not get into this space.
What recent studies have shown us is that there is no such thing as “too fit”. The fitter you are the better you do on pretty much everything.
Here are a couple of studies to show you this.
First, this study in the Journal of American College of Cardiology shows a linear dose-response between fitness and all cause death, cancer death, and cardiovascular death. The least fit are twice as like to get all of these.
An important feature is the continuous dose-response relationship.
In the paper “Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing” they followed more than 122 000 people for more than 8 years. what was cool here was that they had enough people in the study to look at the very fit ones. The top few percent they called “elite fit” older adults.
Here’s what they found:
Results The study population included 122 007 patients (mean [SD] age, 53.4 [12.6] years; 72 173 [59.2%] male). Death occurred in 13 637 patients during 1.1 million person-years of observation. Risk-adjusted all-cause mortality was inversely proportional to cardiorespiratory fitness and was lowest in elite performers (elite vs low: adjusted hazard ratio [HR], 0.20; 95% CI, 0.16-0.24; P < .001; elite vs high: adjusted HR, 0.77; 95% CI, 0.63-0.95; P = .02). The increase in all-cause mortality associated with reduced cardiorespiratory fitness (low vs elite: adjusted HR, 5.04; 95% CI, 4.10-6.20; P < .001; below average vs above average: adjusted HR, 1.41; 95% CI, 1.34-1.49; P < .001) was comparable to or greater than traditional clinical risk factors (coronary artery disease: adjusted HR, 1.29; 95% CI, 1.24-1.35; P < .001; smoking: adjusted HR, 1.41; 95% CI, 1.36-1.46; P < .001; diabetes: adjusted HR, 1.40; 95% CI, 1.34-1.46; P < .001). In subgroup analysis, the benefit of elite over high performance was present in patients 70 years or older (adjusted HR, 0.71; 95% CI, 0.52-0.98; P = .04) and patients with hypertension (adjusted HR, 0.70; 95% CI, 0.50-0.99; P = .05). Extreme cardiorespiratory fitness (≥2 SDs above the mean for age and sex) was associated with the lowest risk-adjusted all-cause mortality compared with all other performance groups.
In actual plain English this means that
- The fitter you were the better
- The elite fit had 5 X less chance of dying than the least fit people.
- This effect is akin to the effects of smoking
- There is still a large effect even from moving from the high fit to the elite fit group
Yes it’s a prospective study. There may be confounders, but it’s unlikely with the effect sizes this large and the known biology involved. In my opinion, the totality of the evidence easily meets Sir Austin Bradford-Hill’s criteria for causal inference.
Why exercise works – exercise physiology
Just as an important note, I think we should do a bit of exercise physiology. First is the concept of Hormesis. Hormesis is the theory that sub-toxic stress is good if we can adapt to it. We end up adjusting our biology to cope with that stress.
We rebuild bigger faster, stronger, more resilient to that stress.
Lose dose radiation is good for us, the toxins in plants may be good for us, cycling between heat and cold stresses in a sauna is good for us, and exercise if we adapt is a stress which can produce a resilient,. stronger system, What doesn’t kill us makes us stronger right?
All good so far. But I think we should be thinking about exercise in two separate stressful modes. They are stressful for completely different reasons.
The first I’ll call anabolic exercise. It’s short and high intensity. You burn glucose and you damage the cells in the body. They respond. This is why weight training, HIT (high intensity interval) training are important and useful. It’s also why you shouldn’t over do this, and should periodise your exercise and allow recovery between hard efforts. It’s my view that many exercisers do too much anabolic exercise and do not allow enough recovery. The damage you create is inflammatory and acutely is good for you. Chronically it’s bad. This is what leads to burnout, sickness, and injury.
What we hardly talk about is catabolic exercise. It’s typically very easy aerobic exercise that creates stress through nutrient stress pathways. That’s why I call it Fasting Mimicking Exercise. It reduces glucose, insulin, IGF-1, inflammation, improves immune function, and generates ketogenic signalling pathways.
Both types of exercise are stressful. Both have hormetic effects. Both are useful.
If you want to exercise catabolically, then you need to know about the Maximum Aerobic Function or MAF.
MAF is where you move from exclusive use of the aerobic energy system to include the increasing use of the anaerobic system. Exercise below this level is easy, feels easy – even if you are unfit – you will just go slower the less fit you are. in practical terms it’s where you have any hint of puffing at all. It’s a pace you could carry on with indefinitely. It’s my view that most exercisers don’t go easy enough to achieve this level.
MAF shouldn’t confused with the anaerobic threshold which is what you sustain in a very hard 30-60 min of intense exercise and above this you can’t speak at all. We are not aiming for this level of hard. In fact, most of us should avoid this except for the occasional high intensity interval training. Its my view that this is where most people exercise when they exercise. No wonder they are tired and find motivation an issue.
I first heard about MAF from Mark Allen (6 time Hawaii Ironman winner) in 1995 at a pro race briefing at the Hawaii Ironman triathlon world championships. I was also a pro athlete there and thought that I may as well ask him what he did to be so awesome.
He was surprisingly forthcoming. He told me about the methods of his coach Dr Phil Maffetone. Allen trained with a heart rate monitor. He did most of his work at or under his MAF threshold. The MAF heart rate is simply:
MAF heart rate = 180 – age
- Add 5-10 beats for high lifetime fitness and being fit
- Subtract 5-10 for sickness, low fitness
Exampleme (Grant, aged 50) = 180-50 = 130 add 10 beats for lifetime experience and high fitness = 140
Example (38 year old female, not very fit) = 180-38 = 142 low fitness = 138
Allen explained that this give him all the fat burning and fitness benefits he needed to be the old champion without all the inflammation and burnout, injuries and tiredness others got. He further explained that Dr Maffetone insisted he maintain a low carb high fat diet to further the process, because high carb, sugar diets made it harder to get the catabolic fat burning benefits from the MAF training.
That was interesting, and completely contrary to what I (a trained scientist) knew about exercise training and nutrition. Remember, I was in the land of Gatorade and threshold training.
So I flipped off his advice as lies and propaganda and keep drinking Gatorade and eating pasta and trained as hard as I could. I got inflamed, sick and fat. Allen went on to win another title!
It was another 17 years before I came to understanding the genius of Maffetone. He was miles ahead of us. Decades later!
Read more about Dr Phil Maffetone here
The MAF test
Now comes the key to this, and what I did with Dr Babor among others. Monitoring your fitness progress using the MAF test is a critical factor in understanding if your exercise is working the way it should. If you exercise and you aren’t getting fitter then what are you doing?
You can read much more on Dr Maffetone’s MAF test on www site here
Maffetone has you walk, jog, or run (depending on your fitness) at your MAF heart rate for 5 miles measuring the time it takes to do each mile. It’s super easy because you are at such a low heat rate, so the test itself hardly feels like a test.
Here are the improvements in MAF test results of a marathon runner over several months. It’s impressive stuff.
The test monitors your progress. The MAF pace training improves you without the stress and risk of hard exercise.
OK, well we are not all marathon runners so let’s move down some levels. First here’s me over a two-month period doing a Thursday run. I opted not to do the 5 X 1 mile test, but just went to a hour or so run-walk on the same circuit. I had a break between lectures on Thursday so went out to get some space. The run was up and down hills and off road in places. I had to walk almost all of the hills to stay under 140 HR.
You will see I improved using MAF training by an incredible 11 min over two months. In other words, I ran the same circuit with the same heart rate 15 percent faster just doing easy jogging and walking. This translates into faster paced running too. I cracked out a 1.25 hr half marathon just doing this. I had been trying prior to this, and too hard. I was only able to run a 1.34 half marathon despite harder training before this.
|Weekly run (hilly bush loop form AUT Akoranga campus around Tuff’sCarter and through Kauri Glen bush)||Run time
@ <140 BPM
|1st March||72 min|
|8th March||69 min|
|6th April||62 min|
|13th April||64 min|
|20th April||62 min|
|27th April||61 min|
In the “How not to get cancer” show I prescribed Dr Babor a MAF exercise program based on fasting mimicking excess principles. I adapted Phil Maffetone’s “MAF” test but used kilometres. It takes less time and yields just as much information. And In my part of the world, who knows what a mile is anyway. A km is way easier to figure out, and it’s how we measure pace when we run/walk
His results astonished even me. In test one on the running track outside my office here at AUT Millennium he managed about 8.30 min per km. That’s pretty pedestrian.
This surprised me because he was going for 90 min hard runs and feel quite tired for his exercise.
Over the next four months he did a similar or slightly less volume, and kept his heart rate under his MAF threshold. He used a heart rate monitor to do so. This meant walking up lots of hills.
Look at the improvement (some due to learning to do the test better perhaps) but he was running 3 min/km faster for the exact same heart rate!
All this by slowing down, and getting catabolic.
As Mark Allen told me. I think this works better when augmented with a low carb diet. That’s the ultimate fasting mimicking, catabolic way to live and therefore the “anti-cancer” combination Dr Babor was looking for in his show.
|Kilometre||Test 1 July 8th
@ <134 BPM
|Test 2 Oct 23rd
@ <134 BPM
Matt Kerr: High performance
I wanted to finish with an actual high performance example. This is Matt Kerr, whom I coach. He’s an elite triathlete. He’s lean, he’s fit, he’s fast.
But he was training too hard, and eating too may carbs in my opinion.
We tested him on our more advanced equipment at our Human Performance labsat AUT Millennium. You get a lot of information about fat burning, catabolic and anabolic exercise, and pace with this sort of testing.
Here’s Matt’s metabolic flexibility curve at high carb, high intensity training at baseline. Remember he is extremely fit. He’s just come off some good shorter racing. But he’s a carb burner. He hardly ever burns fat, and doesn’t do that very well.
Although fit, he had a series of winter injuries I think related to poor training and diet.
He was maxing out at 0.52 g/min of fat burning and doing so at 135 w of power on the bike. That’s slow. That means he relies on carb burning. It means that almost all of the 20 hours training a week he does creates an inflammatory, low immune function, high ROS environment. That’s a recipe for sickness, injury and poor performance especially in long races.
I threw Matt onto a keto diet, MAF train for almost all of his sessions, and included some fasted long rides at a very easy pace.
He could now oxidise 1.1 g/min of fat and could do so at 240 W on the bike. That’s fast and it means training and racing is a clean burning low inflammation, low ROS, high immune function environment
He ended up placing in the top 10 at Ironman NZ in his first race over that distance, in 9 hr 18 min.
OK, this won’t mean much to most of you. For those in that game, its an incredible result. The results for myself, Dr Babor, and Matt show that the same principles apply across all sorts of individuals. I’ve used this with young and old, fast and slow with the same results.
You see, we are all human and we will respond to the stress of catabolic FME. You can’t fail with this if executed properly.
Tools you will need
(disclosures – I have no association with any of these products or companies other than I have bought them and use them myself)
There is just no way around this. If you want to do this method you need an objective measure of effort and heart rate is the easiest. You will need a heart rate monitor of some sort. My preference is an actual smart watch with wrist-based HR. Here’s my Garmin 235 which is the cheaper, but still expensive….
Well there is a way around it. If you can’t afford a heart-rate monitor, just measure the rate by taking your pulse with a watch after different types of exercise to get some idea where your MAF range lies. Believe me its hard to get that really to the level of accuracy you need, but possible I guess.
My watch downloads to a smart app. It’s fun and easy to use.
You can also connect to Strava – a sort of social media for fitness. Its really fun. I have all my friends and family on it. OK, not for everyone but it is cool. Your friends can give you “kudos” which sounds corny but is great.
I also bike lots, swim and surf a bit, and walk a lot. All of these pop up on my smart watch and Strava. Here’s yesterday’s bike in the trainer (I use Zwift, a game type program which is also heaps of fun – you can see my setup in the video at the end of this post).
OK you don’t need to have all the tech stuff I do. But I do love this stuff and it’s a great investment, if you can afford it, in your health and well-being.
How much money do we spend on sickness in our society?
We should dish this stuff out at the doctor. Imagine you go to the doctor and come back with a Garmin 235, a bike, a smart trainer and a Strava account!!
Probably we would save the country money and improve our lot as a society?
Practicalities and final words
Society needs a new perspective on fitness. We need to take it regularly, seriously, but not too hard.
Let’s give up on the term, fitness freak!
If you are going to go this way then get others involved otherwise you’ll be so slow they’ll leave you behind while they all rush off into inflammatory, anabolic exercise land. You have to get your head around the fact that this is slow and easy, and that counterintuitively you get the real benefit by slowing down.
You want the whole peak performance – to be the best you can be – so yes, do the weights and high intensity as well, but not too much.
How much volume is too much? That totally depends on where you are starting from. But very fit humans can easily manage a few hours (or more) of MAF./FME a day. You don’t have to do that unless you are in training for an Ironman triathlon or similar. So start with what feels easy and take it from there. Just keep the heart rate down. Walk when you need to, and leave your ego in a brown paper bag on the kitchen bench before you go out the door. You can collect it when you get back.
I’ll leave you with my short video on “fitness is medicine” (watch out for Bluey, my border collie who is the main star) – enjoy and see you out there (going slowly!)
The other day a new paper modelling a saturated fat tax came out in the journal PlosOne.
In order to improve the population’s diet, the World Health Organization has called for the taxation of foods that are high in SFA.
Oh no not this again! There are very strong socio-economic reasons why such a tax makes no sense, and would probably have the opposite effect of a sugar tax, but before we get to discussing that we’ll look at what the authors did, what they got right, and where they went wrong.
First up, they (all 3 authors are public health analysts, none has published an experiment) are modelling the predicted effect of a tax on fat consumption, using data from Denmark, which had a short-lived saturated fat tax. it was a stupid move for two reasons. First, higher LDL cholesterol is associated with longevity in Denmark – you’ll see how they missed this next. And second, the revulsion against the saturated fat tax and its effect on traditional foods saw both the fat tax and Denmark’s longer-lived sugar tax being thrown out at the next election. So this folly cost them any benefits of their sugar tax. Then, they are modelling the expected rate of CVD (heart attack and stroke) mortality from the predicted changes in LDL cholesterol from substituting polyunsaturated fats (PUFA) for saturated fats (SFA), based on feeding studies.
But hang on – what about the odds of dying from other conditions, like cancer, diabetes, etc? This – all-cause mortality – is not mentioned at all. For all we know we’re shifting the disease burden around, or making it worse overall. Or there may be no benefit for CVD at all either (see admissions below).
The authors get a couple of things right. They acknowledge that there’s no evidence that SFA, by itself, is associated with CVD. Then they turn to the type of computerised remodelling of epidemiological data invented about 10 years ago that looks at replacing one fat with another. In this, it usually (but not always) looks as if replacing SFA with PUFA lowers CVD risk. That’s a hypothesis – so has anyone tested the hypothesis?
Yes they have – and to their credit these authors cite Steve Hamley’s meta-analysis, which corrects errors of data extraction found in others and discusses the confounders in various studies.
A recent meta-analysis, which based their findings on randomised controlled trials, concluded that replacing SFA with PUFA would have no effect on major IHD events . Nevertheless, it is argued that prospective cohort studies find the replacement of SFA with PUFA to be beneficial for the prevention of IHD.
Um, this is epidemiology in reverse. RCTs are the opportunity to test the hypothesis. The Cochrane Collaboration recently summarised the RCT evidence thus, in substantial agreement with Hamley: So are we really to base such big public health changes on no real data of efficacy and a simple hypothesis? How did that end last time with the low fat revolution?
Increasing PUFA probably makes little or no difference (neither benefit nor harm) to our risk of death (moderate-quality evidence), and may make little or no difference to our risk of dying from cardiovascular disease (low-quality evidence). However, increasing PUFA probably slightly reduces our risk of heart disease events and of combined heart and stroke events (moderate-quality evidence). Fifty three people would need to eat more PUFA to prevent one person experiencing a heart disease event, and 63 people to prevent one person experiencing a heart or stroke event. Increasing PUFA may very slightly reduce risk of death due to heart disease, as well as stroke, but harm is possible (low-quality evidence). PUFA probably slightly reduces fats circulating in the blood (triglycerides, moderate-quality evidence but without effects on other lipids or adiposity). The evidence mainly comes from dietary-advice trials of men living in high-income countries.
There’s a very important point here – although PUFA lowers LDL-cholesterol in the short term feeding studies that the tax modelling paper relies on, Cochrane haven’t highlighted that effect in the RCTs. Recently we looked at a study co-authored by Jim Mann where Chinese subjects were fed 40% of calories as soybean oil for a year – a very high PUFA intake. Did that lower their LDL? At the end of the year they had changes to their gut bacteria that Mann thought compatible with an increased risk for bowel cancer and heart disease – but their LDL cholesterol was the same, and they had higher triglycerides.
“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.
So we see that increasing PUFA in real life, which is the intended effect of the tax (or the only way its authors think it might benefit us) does not always produce the results they are predicting from short-term feeding studies done in healthy young white male subjects.
The feeding studies are interesting because they show that some saturated fats (lauric and myristic acids) raise LDL much more than other SFAs. So if the SFA -> LDL -> CVD hypothesis were true, these fatty acids should be the ones most associated with CVD, right?
But no – in every epidemiological study that separates different fatty acids, the cholesterol-raising SFAs are those least associated with CVD. Sometimes, they have a “protective” association.[6,7,8,9]
So what does this mean? Obviously, the cholesterol-raising effect of SFA does not have the same effect on cardiometabolic risk as the cholesterol-raising effect of the genes for familial hypercholesterolaemia. Why anyone still thinks that it can is beyond comprehension – almost every pathway is being influenced in a different way. Yet this crudest of analogies is what we seem to be stuck with as a replacement for the scientific process.
Harm is possible
Cochrane said of PUFA in the RCTs, “but harm is possible (low-quality evidence)”. What does this harm look like in epidemiology?
An increased risk of severe pre-eclampsia (a condition of high blood pressure and proteinuria in pregnancy which can result in seizures) is associated with higher ALA intake in Denmark (canola oil is the main source of ALA there) – RR 1.71
Note that DHA and EPA (fatty fish) have a protective association with severe pre-eclampsia; saturated fat has a protective association with pre-eclampsia which shows a clear dose-response in minimally adjusted (0.63) and multivariable adjusted (0.73) models, but is non-significant in the most adjusted model. Dairy fat is the main source of SFA in Denmark.
This is the country where they actually imposed a saturated fat tax, remember? It’s unlikely they did any modelling around complications of pregnancy beforehand.
Increased risk of melanoma and other skin cancers is associated with higher LA intake in the USA. This is in the NHS/HPFS database, where PUFA usually tends to look better than it does in most other cohort studies; the mechanistic explanation laid out in the paper is a strong one.
Higher intake of omega-6 fat was associated with risk of melanoma (pooled multivariate HR, 1.20; 95% CI, 1.02–1.41; Ptrend=0.03) although the association was attenuated and no longer significant after adjusting for other types of fat simultaneously.
For SCC [squamous cell carcinoma], although total fat intake was not associated with the risk, polyunsaturated fat intake was associated with SCC risk (pooled multivariate HR, 1.16; 95% CI, 1.05–1.28; Ptrend=0.001) (Table 3). Among types of polyunsaturated fat, higher intake of omega-6 fat was associated with SCC risk [HR, 1.23 (1.08, 1.41)]. We also found that cholesterol intake was associated with lower risk of SCC.
Similar associations were also seen for basal cell carcinoma. Co-incidentally or not, the skin cancer death rate in NZ doubled soon after margarine was “legalised” in 1972 and has not declined since despite the slip-slop-slap campaigns and introduction of high-SPF sunscreens. And this is a serious problem, because avoiding sunlight is associated with increased CVD risk – another unintended consequence that modelling will overlook.
How does this compare with a tax on sugary drinks?
The proposed saturated fat tax is not just a different version of a sugar tax, but its opposite. We support a tax on sugary drinks because it targets an unfair price difference – Coca Cola is cheaper than “healthy” alternatives like bottled water, and this price point difference drives people, especially those with less money, towards the drink that will cost them more in the long run. A tax on sugar content goes a small way towards correcting this imbalance. Despite the small extra “penalty” cost to those poor people who still drink SSBs, which some understandably object to, it will tend to make their habits a little more like those of the rich.
The proposed saturated fat tax will do the opposite. Highly saturated fats like coconut oil, butter, and beef and lamb dripping are already about 4x as expensive as the refined seed oils that are high in PUFA. This makes them foods of the healthier, better-off classes. This pricing difference already drives disadvantaged people towards seed oils and the foods made with them – KFC (chicken, higher in PUFA, is also cheaper than other meats), Best Foods mayonnaise, and margarine. If these high-PUFA foods were truly healthier, these populations would be better off as a result – but this is so, so not the case. A saturated fat tax just puts real foods and healthy fats (remember, dairy fat and coconut oil are not even associated with increased disease risk) further out of reach of the poor. It increases the gap between the dietary habits of the rich and poor.
At the very bottom of their paper, the saturated fat tax authors admit that the Danish saturated fat tax (20% on the price of butter etc.) was counter-productive, even according to their own logic.
Finally, a fundamental assumption in our study was that PUFA intake would increase accordingly. This assumption is in line with the dietary recommendations that SFA should be replaced with PUFA [21, 53], and other modelling studies that have assumed the SFA reduction would be replaced by PUFA [14, 16, 17, 20] (see S1 Table). A SFA decrease without a simultaneous increase in PUFA does not seem to be beneficial for health [55, 56]. In Denmark, the decreased SFA intake (ranging from 1.6% in males above age 85 to 4.9% in females aged 55–69) seems to have been accompanied by a changed PUFA intake ranging from a 3.1% decrease in males above age 85 to a 0.3% increase in females aged 60–74 . Therefore, our assumption may lead to an overestimation of the health benefits. Foods contain a mix of SFA, MUFA and PUFA. Therefore, further research needs to examine how this corresponding substitution of PUFA can be assured, rather than a replacement by MUFA or carbohydrates. For instance, a price increase for products high in SFA might need to be coupled with a corresponding price decrease for products high in PUFA.
(If you lowered the price of soybean oil any more you’d be giving it away for free, but OK, whatever you say). Despite this awareness, they still went ahead and published a paper claiming via computerized projections that a saturated fat tax would prevent CVD deaths, even though they had evidence the tax as applied in its only real-life example hadn’t worked as designed (even if you don’t factor in the extinction of the sugar tax it caused). Meanwhile, across the bridge in Sweden an increase in butter consumption, with a drop in carbohydrate intake, has coincided with a halving of the heart attack death rate over the past 15 years.
We’ve said it before and we’ll say it again – public health analysts need to get out among the people they are trying to protect; they need to shop alongside them for a start. The saturated fat tax authors don’t have a clinical intervention to their name. They have no idea what will work in the real world. You can build all the models you like; you can build the Millennial Falcon, for example, but you are never going to see one fly in real life.
 Substituting polyunsaturated fat for saturated fat: A health impact assessment of a fat tax in seven European countries
Johanna-Katharina Schönbach , Wilma Nusselder, Stefan K. Lhachimi
Published: July 10, 2019https://doi.org/10.1371/journal.pone.0218464
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By now you’ve seen these headlines. But what can we learn from the study behind them, and the way it was reported?
The UK Biobank study was a prospective epidemiological study, using the following methods to look at several foods and their association with colorectal cancers:
We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40–69 years at recruitment (2006–10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time.
Here’s a sample of the questionnaire that was used. You’ll see that it collects information about many more types of food than appear in the results. We don’t know how the reported foods were chosen – we’ll return to this later with regard to fibre.
What were the results?
During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4–37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2–24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4–12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk.
76g doesn’t sound like much, but believe it or not was the highest meat and processed meat category in the results. What’s a 20% increase in terms of absolute risk? Because the risk is reported as HR not RR we can’t be exact, but the absolute risk of CRC in the study over 5.7 years was 0.5%, 20% would raise that to 0.6%, which is an increase in absolute risk of 0.1%, or one extra chance in a thousand.
But that summary doesn’t tell us the full story; there are two interesting details in the paper. The first is placed right at the start – this “results” table usually appears once tables for factors like representivity and the confounders at baseline have been displayed, which is the approved way of showing the strengths and weaknesses of the epidemiological process, but not this time. Zoe Harcombe has pointed out that the red meat associations cross the centreline, that is, they are – as always – not statistically significant. (I don’t remember the authors mentioning that to the press).
The other important fact they didn’t mention appears further down the paper. And I mean right down near the bottom, with the details restricted to the supplementary papers!
Supplementary Table 4, available as Supplementary data at IJE online, shows the main results in men and women separately. There was heterogeneity by sex for the associations between colorectal cancer and red and processed meat (Pheterogeneity = 0.008), with a positive association seen in men [HR for each 50-g/day increment in red-meat intake = 1.39 (1.17–1.64)] and no association was seen in women [HR for each 50-g/day increment in red meat = 0.99 (0.83–1.19)]. There was also heterogeneity by sex for red meat (Pheterogeneity = 0.008) and for processed meat (Pheterogeneity = 0.022). There was also heterogeneity by sex for alcohol, with a positive association seen in men [HR for each 10-g/day increment in alcohol intake = 1.12 (1.08–1.17)] and no association seen in women [HR for each 10-g/day increment = 0.99 (0.93–1.06), Pheterogeneity = 0.002]. There was no heterogeneity by sex for the associations between fish, dairy milk, cheese, fruit, vegetables, fibre, tea or coffee and colorectal cancer.
So of all the associations tested, only fibre from grains (14% lower risk, remember) had any association with colorectal cancer risk in women, or the same risk as seen in men.
We’ve looked at several of the reports on this study in the media, and the study authors don’t mention women in any of them that we’ve seen. The results are reported as if they apply to everyone regardless of sex. Usually a reporter might pick up on such a detail and ask a question about it, but in this case the study authors hit the media before their study was posted online, so reporters didn’t have a chance to read it.
It’s an important and worrying omission for several reasons:
Women have been poorly served by medical science, which has often used male subjects for convenience, arriving at results which were just wrong for women. Caroline Criado Perez has recently published a book on this problem, Invisible Women, a section of which was published in Canvas magazine recently (March 23, 2019). In the UK Biobank study the authors had a large cohort of women – there were more women than men in the study – but as far as publicity was concerned they completely ignored the women’s distinctive results.
Women are more likely to be health-conscious than men (so far as we know, meat-eating hasn’t been associated with increased disease risk in the “health conscious” subgroups of the cohorts in any studies which apply this test). We know this generalisation is true from our work with What The Fat? and PreKure. This means that women are more likely to be aware of, and be influenced by, health messages in the media.
Women are more likely to be harmed by meat avoidance, because rates of iron and zinc deficiency are higher in women. B12 deficiency is also well worth avoiding. Fiona Greig, Beef and Lamb New Zealand’s well-informed head of nutrition, makes an especially good case in the Herald report on this study considering that she didn’t have access to the paper when she was asked to respond. Dr Felice Jacka who has studied the links between diet and depression for several years, including with a successful RCT, recommends 65-100g of red meat a day as part of the protocol for preventing anxiety and depression, which are strongly associated with meat avoidance. Misinforming women about the health effects of meat-eating has the potential to do real harm; let’s not forget that New Zealand is facing a mental health crisis, and that our government has set “wellness” as a target.
An additional reason that the null association in women should have been reported is, that it informs our confidence in the association being causal. Consistency and coherence are Bradford Hill criteria useful in assessing the links between association and causation. Completely different results for men and women are inconsistent (as are the results of other studies with no CRC associations for red meat, such as EPIC-Europe, or no cancer association for processed meat, such as the recent Seventh Day Adventist study). Nor does this give a coherent picture; this is not how “carcinogens” are expected to behave.
What about fibre?
In both men and women, grain fibre was associated with a 14% lower risk of colorectal cancer. Does this mean we all need to eat wholegrains? Not so fast – remember that the questionnaire collected data on many foods, including “white” carbs – white bread, white rice, pasta, pastry, and so on, as well as sugar. As the study was a UK study, total fibre intakes were pretty low by world standards. In the UK white bread is supplemented with folic acid (though this only became mandatory in 2018), and long-term exposure to high doses of folic acid (i.e not its temporary use in pregnancy, which is safe and beneficial) is also believed to be something of a risk factor for colorectal cancer (one reason folic acid fortification of bread, though usual, isn’t yet mandatory in NZ). Folate, the slow-release form of folic acid found in whole foods, is not thought to increase risk, and wholegrain bread doesn’t need to be fortified.
So were refined carbs, like white bread and sugar, associated with CRC in UK Biobank? We just don’t know; maybe this will be the subject of a future paper. In the EPIC-Italy cohort, from 2017, we find that “High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers, but decreased risk of stomach cancer; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk.” Which figures.
Because, what do we know with certainty about the causes of increases in CRC risk? Genetics plus ageing mean that cancer risks are never non-existent, but there are three factors the avoidance of which should keep them low –
High insulin. Fasting insulin is associated with CRC risk, and central obesity, type 2 diabetes, and the metabolic syndrome increase the risk of colorectal cancers. “Greater WC [waist circumference] and WHR [waist-to-hip-ratio] were significantly associated with increased risk of total colorectal cancer (WC: RR 1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR 1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR 1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42).” 
Micronutrient deficiencies. Low selenium status, and low levels of PLP, the active form of B6, have been associated with increased CRC risk, and no doubt other micronutrient associations can be found. New Zealand is known for its low soil selenium status and high rates of bowel cancer. The risk is highest in the South Island, where selenium levels are lower because more imported food is eaten in the North.
Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82–0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72–0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86–1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.
Carcinogen exposure. This is the obvious one, one that is easy to overlook because it’s difficult to measure in a FFQ. But think about who works more in these kinds of industries – men or women? What are they likely to eat? Are these industries that will attract many vegans or vegetarians?
This work pointed out increased risks of colorectal cancer for labourers occupied in industries with a wide use of chemical compounds, such as leather (RR = 1.70, 95%CI: 1.24-2.34), basic metals (RR = 1.32, 95%CI: 1.07-1.65), plastic and rubber manufacturing (RR = 1.30, 95%CI: 0.98-1.71 and RR = 1.27, 95%CI: 0.92-1.76, respectively), besides workers in the sector of repair and installation of machinery exposed to asbestos (RR = 1.40, 95%CI: 1.07-1.84). 
And maybe it’s the oil too – in the recent China study RCT co-authored by Otago’s Jim Mann, a diet high in soybean oil, which is toxic to gram-positive bacteria, caused changes in the gut microbiome that have been associated with a higher CRC risk. It’s early days for this question, but we don’t recommend the extensive use of vegetable seed oils for a number of good reasons, hence “low carb healthy fat”.
The question of meat
We’re not concluding that meat, along with some other far less nutritionally valuable foods, can’t contribute to colorectal cancer, in men or women. Cooking methods might matter, as charred meat contains small amounts of chemicals called HPAs, which are carcinogens in high concentrations (interestingly HPAs are neutralised in the gut by acrolein, a carcinogenic toxin in its own right at high levels, which is formed by the burning of fat, by the beneficial probiotic Lactobacillus Reuteri, and by normal metabolic processes – clearly an example where the dose, and the context, makes the poison). High intakes or serum levels of iron are also possibly cancer promoting, but the differences between meat intakes in UK Biobank don’t seem large enough to be explained in this way. Nor does iron retention explain the difference between men and women, as the average age at the start of the study was 55 and the majority of women had passed through menopause. Blood donation, which significantly lowers iron levels, is associated with a reduced risk of some diseases – but not colorectal cancer.
It may also be relevant that some processed meats, especially those which go through “wash” processes, are very poor sources of micronutrients when compared with their unprocessed equivalents, with vitamins and minerals being lost during processing. Meat is a source of many of the micronutrients and amino acids involved in detoxification and antioxidant defense, including selenium. Thus if red meat does have an effect on cancer, this is likely to be bidirectional, which would be less true for some processed meats.
If anyone on a low carbohydrate diet is convinced by the reduced CRC risk associated with grain fibre, which is also seen in other studies for other diseases, and unconvinced by the argument that this just shows the same benefit of avoiding refined grains that we’re already enjoying, organic oat bran can be added to mince dishes such as patties and meatloaf, and makes an ideal binder.
Note that the richest animal food sources of saturated fat, the dairy products, were not associated with CRC in this paper (and usually have protective associations); higher HDL and the log[TG/HDL] ratio (AIP) were associated with lower CRC risk in EPIC-Europe in fully adjusted models, as was higher cholesterol before adjustment.
(Oh, also – fibre from fruit and vegetables not associated with cancer risk – what’s that about, 5+? It’s a fairly common finding in epidemiology, weak or no protective association for fruit and/or vegetables, but it never makes the news. When it contradicts the received version, we’re supposed to ignore science. So, eat your veges – after all, you have to eat something, and they’re going to be better for you than refined carbs!)
1] Kathryn E Bradbury, Neil Murphy, Timothy J Key, Diet and colorectal cancer in UK Biobank: a prospective study, International Journal of Epidemiology, , dyz064, https://doi.org/10.1093/ije/dyz064
2] Sieri S, Agnoli C, Pala V, et al. Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study. Sci Rep. 2017;7(1):9757. Published 2017 Aug 29. doi:10.1038/s41598-017-09498-2
3] Dong Y, Zhou J, Zhu Y, et al. Abdominal obesity and colorectal cancer risk: systematic review and meta-analysis of prospective studies. Biosci Rep. 2017;37(6):BSR20170945. Published 2017 Dec 12. doi:10.1042/BSR20170945
4] Hughes DJ, Fedirko V, Jenab M et al. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. International Journal of Cancer, Volume136, Issue5, 1 March 2015 Pages 1149-1161
First published: 09 July 2014 https://doi.org/10.1002/ijc.29071
5] Oddone E, Modonesi C, Gatta G. Occupational exposures and colorectal cancers: a quantitative overview of epidemiological evidence. World J Gastroenterol. 2014;20(35):12431–12444. doi:10.3748/wjg.v20.i35.12431
6] Engels C, Schwab C, Jianbo Zhang J, et al. Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin. Scientific Reports volume 6, Article number: 36246 (2016).
7] Zhang X, Ma J, Wu K, Chan AT, Fuchs CS, Giovannucci EL. Blood donation and colorectal cancer incidence and mortality in men. PLoS One. 2012;7(6):e39319. doi:10.1371/journal.pone.0039319
8] Sobiecki, J.G. Vegetarianism and colorectal cancer risk in a low-selenium environment: effect modification by selenium status? A possible factor contributing to the null results in British vegetarians. Eur J Nutr (2017) 56: 1819.
9] van Duijnhoven FJ, Bueno-De-Mesquita HB, Calligaro M et al. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition.
Gut. 2011 Aug;60(8):1094-102. doi: 10.1136/gut.2010.225011. Epub 2011 Mar 7.
This is well worth the watch. Some NZ twists in here from our team and the battles going on (see the last post for more on the spoiler plays against low carb and diabetes reversal coming out of NZ that were mentioned by Aseem)
We were surprised to hear this Radio New Zealand interview with Jim Mann regarding a Chinese study he co-authored. 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.
“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.
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. 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.
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.
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. 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. A 2018 review  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 (Kabara et al., 1972; Kankaanpää et al., 2001; Kodicek, 1945; Nieman, 1954). The primary modes of killing include permeabilization of cell membranes (Greenway and Dyke, 1979) and interference with FA metabolism (Zheng et al., 2005). Affected microbes are predominantly Gram-positive bacteria including the genus Lactobacillus (Nieman, 1954). Lactobacilli are particularly important as they are considered beneficial members of the human small intestine (Walsh et al., 2008; Walter et al., 2007; Walter et al., 2011). They have been shown to be growth inhibited by the specific FAs present in SBO (Boyaval et al., 1995; De Weirdt et al., 2013; Jenkins and Courtney, 2003; Jiang et al., 1998; Kabara et al., 1972; Kankaanpää et al., 2001; Kodicek, 1945; Raychowdhury et al., 1985). 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 (Walter et al., 2011). 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 (Reuter, 2001). Today, however, it is found in less than 10% of humans in the USA and Europe (Molin et al., 1993; Qin et al., 2010; Walter et al., 2011), yet it is present at a reported 100% prevalence in rural Papua New Guineans (Martínez et al., 2015).
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).
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.
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. 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.
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.
 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
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 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.
 Kodicek E. The effect of unsaturated fatty acids on Lactobacillus helveticus and other Gram-positive micro-organisms. Biochem J. 1945;39(1):78-85.
 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
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 Ioannidis JPA. The Challenge of Reforming Nutritional Epidemiologic Research. JAMA. 2018;320(10):969–970. doi:10.1001/jama.2018.11025
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SCIENCE IN A MINUTE: @Caryn Zinn Nutrition reviews the latest Lifestyle Medicine research released two weeks ago in the British Medical Journal (BMJ) on weight-loss maintenance.
Which diet works best for maintaining weight loss? Find out…
What’s more important to you – your left arm or your right foot? What would you rather keep if you had to lose one or the other?
Well, here’s my opinion in the video below and longer blog here
Actually it’s all about how we need to talk about fitness more. Fitness is medicine. Enjoy…and get fit!
You will see yourself linked to Prekure’s www site. Prekure – “prevention is cure” is a social enterprise I’m part of with 8 other health professionals from oncology to public health to general practice to pharmacy.
We are hoping to make a dent in medicine – to move from drugs as frontline treatment, to lifestyle as first line medicine. The social arm offers free lifestyle medicine programs which really work, available for everyone. We are also doing medical education training for health professionals – in lifestyle medicine, of course. We want to bring today’s evidence to the front line of healthcare – its compelling.
We’ve just got going. Stay tuned and please join our community to change medicine to “prevention as cure”. More to come.
Prekure’s social links below