by Tim Noakes
4. There is no evidence that blood cholesterol concentration during life can predict the extent of coronary artery disease at death
If blood cholesterol concentration determines heart-attack risk, then autopsy studies should show a direct linear relationship between the extent of coronary artery disease at death and pre-morbid blood cholesterol concentration. But more than 19 studies, using many different methods, have failed to establish such a relationship. This has led W.R. Ware to conclude:
The large number of null results for the association between serum LDL cholesterol levels and the prevalence or progression of both calcified and non-calcified plaque in the appropriate vascular bed and involving large numbers of men and women over a wide range of age, ethnic background, plaque burden and cholesterol levels cannot be easily dismissed. If the hypothesis is false, this has a significant impact on currently held views regarding risk factors and therapeutic interventions in the case of individuals who are asymptomatic, that is, issues associated with primary prevention. Also, if the hypothesis is false, then the use of changes in LDL as a surrogate marker for judging the importance of various risk factors for silent atherosclerosis and thus coronary artery disease can be called into question.46
The point is that your blood cholesterol concentration gives you absolutely no information about the state of your coronary arteries. However, your level of IR and the extent to which your daily carbohydrate intake has raised your HbA1c value will, in my opinion, prove to be excellent markers of how badly your arteries are likely to have been damaged.
For example, an HbA1c of 10 per cent in a person with uncontrolled T2DM increases the risk of having a limb amputation tenfold; the risk of any endpoint related to the disease fourfold; and the risk of having a heart attack or stroke twofold.47 Measuring ‘cholesterol’ in patients with T2DM will have no such predictive value and is essentially useless.
Figure 17.8
Hazard ratios for any endpoint related to diabetes (Panel A); for death related to diabetes (Panel B); for microvascular endpoints – kidney, heart, brain, eye, limb (Panel C); and for amputations or death from peripheral vascular disease (Panel D). Note that at HbA1c values greater than 8 per cent, the hazard ratios for all these outcomes is more than 2.0. Compare with predictive value for cholesterol and risk for developing heart disease (Table 16.2). Redrawn from I.M. Stratton et al., ‘Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes’48
5. A low blood cholesterol concentration predicts a shorter life expectancy and increases risk for developing a range of diseases
If the body produces cholesterol solely to damage our coronary arteries and to kill us from heart disease, it follows that the lower the blood cholesterol concentration, the longer we will live.
But the evidence is clearly the opposite. As described in Chapter 7, low blood cholesterol concentrations are associated with a range of adverse health outcomes, including a shorter life expectancy and a greater risk for developing cancer and probably dementia. This is likely because cholesterol serves so many vital functions in the human body, such as:
Maintaining the stiffness and stability of cell walls.
Essential for the synthesis of neurotransmitters for propagation of nerve impulses through neurons.
Essential for the production of enzymes and hormones, including aldosterone, cortisol, oestrogen, cortisone, progesterone, testosterone and ubiquinone.
Essential for the synthesis of vitamin D3, which is responsible for proper bone calcification.
Essential precursor of other molecules that are important for proper bodily functioning, including the production of bile.
By now it should be clear that all the evidence incriminates carbohydrates and IR as the key drivers of our current epidemics of ill health. Table 17.3 lists the blood parameters that really predict the extent to which one is insulin resistant, and hence one’s real risk for developing the diseases linked to IR.
Table 17.3: Blood values, blood pressures and body mass indices indicating different levels of IR
Blood parameter
Insulin sensitive
Borderline
Insulin resistant/T2DM
HbA1c %
4.5
5.5
>6.0
Gamma-glutamyl transferase activity (U/L)
<45
>45
>100
Fasting insulin concentration (mIU/L)
<2.0
2.0–10.0
>10.0
Fasting glucose concentration (mmol/L)
<5.0
>5.5
>6.5
Fasting triglycerides (mmol/L)
0.5
1.0–1.5
>2.0
HDL-cholesterol concentration (mmol/L)
1.6
1.4
1.2
Fasting total cholesterol concentration (mmol/L)
Of no value in determining extent of insulin resistance.
Minimal value for predicting risk of future heart attack.
Fasting LDL-cholesterol concentration (mmol/L)
Of no value in determining extent of insulin resistance.
Minimal value for predicting risk of future heart attack.
Blood pressure (mm/Hg)
<120/80
140/90–150/95
>160/100
Body mass index (kg/m2)
<24
24–28
>28
Reproduced from The Banting Pocket Guide, Cape Town: Penguin Books, 2017
We might never have known that it is carbohydrate, and not fat, that is the cause of our ill health were it not for the catastrophic change in our diet brought about by the introduction of the 1977 Dietary Guidelines for Americans. The idea that humans should increase their carbohydrate intake by eating more cereals and grains and less animal produce was not born from evidence that this would make us healthier. Nina Teicholz and Dr Zoë Harcombe made this clear in their testimony during the HPCSA hearing (Chapter 13). Instead, it followed the decision by President Richard Nixon in 1972 that in order to win re-election, he needed to reduce the cost of food and improve the wealth of US farmers.
To achieve this, he appointed Earl Butz as his secretary of agriculture. Butz’s solution was to reward farmers in the Midwest so that they would produce wheat, maize and soy in ‘industrial’ amounts. As a result, US grain production increased dramatically to the point where, today, the US no longer has any reserve storage capacity for its grain surplus. Having industrialised the production of these grains, the next challenge faced by US politicians was how to sell this relatively cheap product not just to Americans, but also to the rest of the world. The solution was the 1977 US dietary guidelines, which demonised the high-fat foods that had allowed humans to become human, and romanticised the high-grain (poor people’s) diet that, as I have shown, so damaged the health of the Egyptians and the poorest people on the Indian and African continents.
Removing fat from the diet also reduced the palatability of our foods. In a quest to return some flavour, food manufacturers discovered that by sweetening foods with sugar or high-fructose corn syrup, they could induce an addictive eating response.49 As I wrote in The Real Meal Revolution: ‘But one facet of processed foods is held sacrosanct by the industry. Any improvement to the nutritional profile of a product can in no way diminish its allure, and this has led to one of the industry’s most devious moves: lowering one bad boy ingredient like fat while quietly adding more sugar to keep people hooked.’50
Over the next 35 years, the 1977 Dietary Guidelines for Americans produced a progressive and sustained increase in the addictive consumption of more and more carbohydrates.51 This higher carbohydrate intake produced a 7–21 per cent increase in daily energy intake of men and women in the US, associated with large increases in the body mass indices of both genders.
Figure 17.9 on page 353 shows that following the introduction of the 1977 US dietary guidelines,
the contribution of carbohydrate to the US daily energy intake increased from about 40 to 65 per cent. This increase was associated with the beginning of the obesity/diabetes tsunami that has since engulfed the world. I think there are two explanations for why this has happened.
The first is the addictive nature of sugar, which has hijacked the appestat controlling what we eat. The mechanism for this is fully described in The Real Meal Revolution and I will not repeat it here. The simple explanation is that carbohydrates make us hungry, whereas fats and proteins satiate. Chronic overconsumption of calories, especially carbohydrate calories, induces persistent hyperinsulinaemia that worsens IR, producing all the biological consequences of that condition.
Figure 17.9
Left panel: changes in percentage calories from dietary fat and carbohydrates since adoption of the 1977 Dietary Guidelines for Americans. Note the dramatic changes between 1965 and 1999, and that in 1965 the percentage fat intake was 45% and carbohydrate intake 38% (circled). Right panel: there has been a progressive increase in the US average body mass index since the adoption of the guidelines. The logical assumption is that the increased carbohydrate consumption (left panel) caused the increase in body mass index (right panel). Redrawn from E. Cohen et al., ‘Statistical review of US macronutrient consumption data, 1965–2011’; L.S. Gross et al., ‘Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: An ecological assessment’52
The second factor has yet to be acknowledged by any biologist as far as I am aware. Here you will read it for the first time.
In Chapter 16, I described how the common ancestors of humans, chimpanzees and bonobos must have been hindgut fermenters. Although on occasion they ate fruit, which would have provided simple sugars (glucose and fructose) that travelled in the bloodstream directly to the liver in the portal vein, their main carbohydrate foods were in the form of cellulose.
Critically, microbial activity in their voluminous hindguts would have fermented the ingested carbohydrate (cellulose) anaerobically into volatile fatty acids, predominantly acetic, propionic and butyric acid. While superficially our hominin ancestors might have appeared to be eating high-carbohydrate diets, as a result of this microbial fermentation they were, in fact, eating diets high in fat, most of which was saturated. In fact, 60–70 per cent of the energy absorbed from the intestine in chimpanzees and gorillas is in the form of saturated fats. It is not an exaggeration to state that the large bowel of these great apes is an organ designed specifically to generate saturated fat.
The end result is that all mammals, carnivorous or herbivorous, subsist on high-fat diets. The sole exception is humans, who were advised to adopt a high-carbohydrate diet in 1977.
‘Clearly from the standpoint of the host animal, VFAs [volatile fatty acids] are the important product of fermentation,’ writes Richard Bowen of Colorado State University. ‘These small lipids are used for many purposes, but the paramount importance of VFAs to herbivores is that they are absorbed and serve the animal’s major fuel for energy production’,53 providing ‘greater than 70% of the ruminant’s energy supply’.54
The first crucial point is that the ruminant’s liver generates the glucose it requires from volatile fatty acids. As a result, ruminants are never exposed to high blood glucose concentrations following the ingestion of their high-carbohydrate (cellulose) diets, as now occurs in modern humans ingesting readily digested carbohydrates every few hours.
The second key point is that in their natural state, hindgut fermenters do not absorb large amounts of glucose directly into the portal vein and hence directly into the liver. Over the last two to four million years, our hominin ancestors reduced their reliance on dietary cellulose, replacing it with animal fat and protein, while the large bowel shortened (Figure 16.1). Until very recently, humans have had no long-term experience of the effects of dietary carbohydrates absorbed directly from the small bowel into the portal vein.
Crucially, we now know that if these increases happen repeatedly every few hours for decades on end, our IR worsens to the point at which insulin does not produce the desired outcome, however much is secreted. The result is T2DM. It is therefore IR, and not heart disease, that is our greatest medical threat. As a result of the promotion of the 1977 US dietary guidelines and the romanticisation of the health benefits of the high-cereal diet, humans must now face – for the first time in the six million years of our evolutionary history – the frequent rapid delivery of glucose into the portal vein. For the first time, we must cope with repeated rapid rises in blood glucose and insulin concentrations each time we eat the ‘displacing foods of modern commerce’.
IR is now certainly the most prevalent medical condition in the world, yet it is not taught or discussed in most medical schools.
An interesting part of Weston Price’s work was that he did not find any populations existing on predominantly high-carbohydrate diets. Rather, in all the populations that he studied, fat and protein were the major contributors to daily caloric intake, as they were in our more ancient ancestors (Homo erectus and the Neanderthals), and in modern humans such as the Inuit, the Masai and modern foragers (Table 17.4). Only in the last 40 years since the introduction of the US dietary guidelines have carbohydrates begun to provide more than 40 per cent of our daily calories.
Table 17.4 Changes in dietary fat, protein and carbohydrate intakes in the course of human evolution
Fat
Protein
Carbohydrate
Gorilla (ingested)
3
24
73
Gorilla (absorbed)
60
Chimpanzee
3
21
76
Australopithecus africanus
?
?
?
Homo habilis
?
?
?
Homo erectus55
44
33
23
Neanderthals56
74-85
15-26
0
Homo sapiens – Masai
66
14
20
Homo sapiens – Inuit
48-70
14
16-38
Homo sapiens – modern foragers57
28-58
19-35
22-40
Homo sapiens58
33
14
53
Note that the proportion of energy derived from dietary fat has fallen, while that from carbohydrate has increased over the past few million years, but with the greatest change since 1977 (modern Homo sapiens)
Nevertheless, there are populations who are as healthy as those described by Price despite eating higher-carbohydrate diets. The 2 300 inhabitants of the small island of Kitava off the east coast of New Guinea eat a diet based on tubers (cassava, yams, sweet potatoes and taro) and fruits (bananas, papaya, guavas, pineapple, mangoes and watermelon), supplemented with fish and coconuts. Despite their lifelong high-carbohydrate diet, Kitavans remain insulin sensitive for life,59 and are therefore quite different from the Australian Aborigines, who are insulin resistant, apparently on a genetic basis.
The Kitavans are most likely an unusual population. This is important, because the majority of the world’s population is more likely insulin resistant60 (because they respond to an increased refined-carbohydrate intake by developing obesity and T2DM). Extrapolating the Kitavan experience or that of the Tsimané of Bolivia61 to global populations may therefore lead to dietary advice that is the opposite of what is likely to be the healthiest.
Basically, insulin resistance, previously termed ‘the thrifty genotype’,62 is a condition in which the insulin secreted normally in response to the carbohydrate, and to a lesser extent the protein, content of a meal fails to act appropriately on all the (insulin-receptive) bodily organs. The key abnormality is when the insulin fails to suppress
glucose production by the liver (liver insulin resistance). In this case, following the ingestion of a carbohydrate meal, the liver continues to produce an excess of glucose. This causes blood glucose concentrations to remain elevated, stimulating further insulin secretion and producing hyperinsulinaemia (excessive levels of insulin circulating in the bloodstream).
The skeletal muscles and liver also have a reduced capacity to take up and store blood glucose (in the human form of starch – namely, glycogen). Instead, the excess glucose is converted to triglyceride for storage in the liver, producing NAFLD in the long term. The NAFLD in turn produces atherogenic dyslipidaemia, which leads to the disseminated obstructive arterial damage that is the characteristic feature of T2DM.
Once the fat cells in the adipose tissue become insulin resistant, they will fail to store fat appropriately, causing the continuous release of their contained fatty acids into the bloodstream; this fat will also end up in the visceral organs, including the liver and pancreas, worsening the IR.
But it is not the fat that causes the T2DM; rather the opposite. It is the high-carbohydrate diet in those with IR that sets up and perpetuates this vicious cycle.
Let us now look at how IR likely arose as a common human trait and why it is so damaging to our health in the presence of a high-carbohydrate diet.
1. It begins in the third trimester
Humans are the only land-based mammals whose babies are born with significant amounts of subcutaneous body fat. Since our nearest relatives, the chimpanzees and bonobos, do not produce fat babies, humans must have developed this adaptation in the past six million years. But to what possible advantage?
The answer is that the subcutaneous fat of the newborn provides the energy and the chemical building blocks for the rapid growth of the neonatal brain, as shown in Figure 16.3 on page 314. We know that this fat layer is laid down in normal pregnancy in the final trimester (12 weeks).