Fructose and Health: Book review of 'Nature wants us to be fat'

16 October 2024 by Kevin Handreck

Book Review: Nature wants us to be fat (The surprising science behind why we gain weight and how we can prevent – and reverse – it')
by Dr Richard Johnson, BenBella Books, 2022

This book is a summary of more than 20 years of research by Dr Johnson and his many collaborators. This research has tried to answer the fundamental question: why do we develop obesity and related diseases such as diabetes, heart disease, high blood pressure, and more? Dr Johnson takes us step by step through his ‘why’ and how’ questions, at each step showing a conclusion that came from his research, and the next questions that flowed from that conclusion. It is a fascinatingas fascinating journey which, I believe, really does give an answer to his fundamental question. I will now state his conclusion, then summarise some of the science that supports his conclusion.

His research has identified a biological process that animals use to help them survive. This process is most commonly triggered by the food they eat, of which fructose turns out the be especially important, although other foods stimulate it as well. He calls this process the survival switch, because it turns on a whole series of physical and metabolic changes, as well as behaviours, that protect animals in nature when food is not available or is in short supply.

Some Background

Our ancestors survived by being able to fatten up during times of plenty so that they had ample fat reserves for times when food or water was in poor supply. Stored fat is a source of water when it is burnt.

It looks like we are programmed to put on fat when ample food is available, or, as Dr Johnson says in the title of this book: Nature wants us to be fat! That was all very well when food was sometimes in short supply, but in the current situation of 24/7 access to abundant food in the developed and developing world, a survival mechanism has become a cause of chronic disease. It has turned into a fat switch.

Overnutrition does lead to obesity, but the blame is not that we exercise too little. The root of the problem is biological; in these modern times of abundant food options, we keep activating the survival switch.

What triggers the biologic response? FRUCTOSE is the main trigger. For hibernating animals (like bears), massive intake of fructose triggers massive food intake and a high production of fat

Fructose

Fructose causes insulin resistance, elevation of blood triglycerides, and other features of metabolic syndrome (obesity, abdominal fat, elevated blood pressure, fatty liver). Insulin resistance is a major survival response in animals that may at times lack food and water. The resistance resolves once the fat that is a feature of insulin resistance is burnt off. In metabolic syndrome (MetS), the resolution does not happen so the insulin resistance continues.

Fructose is metabolised to uric acid. It is the uric acid that increases blood pressure (as well as leading to gout). Fructose is unique amongst sugars in this effect of raising uric acid level.

In one trial, when mice were given fructose, it took a few weeks before they increased their food intake. Then they appeared to be permanently hungry; they also decreased their metabolism. High fructose intake caused all the symptoms of MetS - weight gain, fat accumulation, fatty liver and insulin resistance, elevated BP, increased blood triglycerides and markers of inflammation, reduced HDL-C.

In mice that could not metabolise fructose, a high intake of HFCS did not cause insulin resistance or fatty liver. So, fructose is the culprit in soft drinks. Fructose does not itself stimulate insulin release, but when it is metabolised, it activates the survival switch, which over time causes the development of insulin resistance. The cause of Metabolic Syndrome is FRUCTOSE.

Even when rats were on a calorie restricted diet, they developed diabetes and fatty livers when given fructose, but not when given starch. These effects were mediated via leptin resistance: the eating off-switch is inoperative or toned down.

The main effect of sweet taste is to encourage intake of sweet foods but, we get fat from sugar even if we cannot taste it! Sugar is addictive; it triggers release of dopamine.

The preference for sugar is dependent on metabolism of fructose in the intestines, while fructose’s ability to cause obesity and insulin resistance stems from its metabolism in the liver.

The mechanism by which fructose stimulates foraging

A high intake of fructose actually reduces energy supply (ATP) to our cells. While the metabolism of fructose produces a small amount of ATP, much of this is used in this metabolism. The net effect is that ATP levels fall precipitously if a lot of fructose has to be metabolised. Lowered ATP levels trigger hunger and foraging: the survival switch.

When ATP is used for energy, it is converted to ADP, which can then be converted back to ATP. But with fructose, the ADP is broken down into AMP and then into uric acid. This uric acid also directly reduces ATP production through its oxidative stress effect on mitochondria. This stress blocks the burning of fatty acids.

All of this information is summarised in a table (headed The Survival Switch) on pp 59-60 of the book. Dr Johnson shows how the biological response to fructose ties together: hunger, craving, foraging behaviour, increased food intake, reduced metabolism when at rest, fat accumulation, glycogen accumulation, thirst, insulin resistance, increased blood pressure, salt retention, low-grade inflammation, reduced oxygen needs. To quote: “Mother Nature is smart. Consuming fructose tricks an animal into thinking that energy stores are low, even when it has plenty of untapped energy in the form of fat. This drives the animal to increase its fat stores and triggers a host of other metabolic responses that aid survival in a crisis.” and “We have disrupted this beautiful balance by finding ways to eat fructose all year long.”

Further Background

Two mutations that were life-saving in pre-agricultural times, now cause disease.

Approximately 65 million years ago there occurred a mutation in the common ancestor of lemurs and apes that wiped out their ability to make vitamin C. This reduced their ability to combat oxidative stress. This in turn triggers the survival switch so that much fat is produced from fructose. So, a starving animal with low vitamin C level would maximise fat production from fructose, and therefore be more likely to survive than an animal that could make its own vitamin C. Overweight people tend to have low vitamin C levels. Therefore, improving vitamin C levels via fructose free alternatives is a critical component for reducing Metabolic Syndrome.

In a second mutation, about 15 million years ago, the apes that had escaped back to Africa from a cooling Europe, lost their ability to make uricase, so their uric acid levels rose. Higher uric acid levels would increase oxidative stress and activate the survival switch, so their livers could make more fat from the same amount of fructose. This uricase mutation only raised uric acid levels modestly, to cause fattening but not obesity. But with a high intake of fructose, uric acid levels rise much more, and so leads to obesity.

Glucose is not Innocent

High glycaemic foods lead to fructose production in our bodies, through the polyol pathway (via sorbitol). The polyol pathway activates the survival switch when fructose-rich foods are not available.

Mice: high intake of glucose led to a high production of fructose in their livers, and obesity. The fattening effect of glucose is due to the fructose that the body makes from that glucose.

Sugar is as addictive as alcohol. Both cause fatty liver and cirrhosis. Alcoholics are usually addicted to sugar. Both tend to cause dehydration. Alcohol stimulates fructose production, via activation of the polyol pathway.

The craving for alcohol and its ability to cause liver disease both stem from its stimulation of fructose production, which then turns on the survival switch.

Effect of Salt and Dehydration

Salty foods produce dehydration; this increases fructose production and so fat and Metabolic Syndrome, originally as a survival mechanism, but now not. Most of salt’s negative effects are due to stimulation of fructose production. In trials, high salt was 11-12 g/d; he recommends 5-6 g only, or a bit more if one is on a low carb diet.

The author also noted that it was observed that obese people are often chronically dehydrated, and have high vasopressin levels so that urine production is reduced.

Contrary to what soft drink manufacturers would have us believe, soft drinks do not quench thirst: they leave us wanting more. Increasing water intake by dehydrated people blocks obesity and insulin resistance.

MSG

Umami- MSG also stimulates food intake via the survival switch – but this is a small effect unless one is eating a lot of glutamate via soy.

Fructose causes many chronic diseases and health conditions

Dr Johnson takes a whole chapter (6) to give detail of the research that supports his conclusion that fructose has a causal role in most chronic diseases: gout, T2D, hypertension, stroke, CVD, CVA (stroke), non-alcoholic fatty liver disease, chronic kidney disease, cancer. He says that the evidence that fructose-containing sugars are the cause of T2D is overwhelming.

Here are the highlights:

ADHD: Fructose consumption raises uric acid levels and so increases foraging activity, including impulsivity, novelty-seeking and risk-taking and decreased ability to deliberate (think before acting). ADHD and bipolar disorder have characteristics that are closely similar to this survival switch effect. ADHD incidence is highest in countries with the highest sugar consumption.

In children, the higher the number of soft drinks consumed each day, the greater the level of hyperactivity (and uric acid level).

He also observed, bipolar subjects ingested more sugar and refined carbs than the general population. Lithium reduces bipolar symptoms by increasing the excretion of uric acid in the urine, so reducing its concentration in blood. Bipolar individuals make fructose in their brains.

The occurrence of obesity, dental caries and spinal distortion in a human population is directly related to the amount of sugar (from any source) consumed. Affordable sugar increases use, markedly.

Fructose versus glucose: same weight gain but much more Metabolic Syndrome symptoms from fructose. Two weeks of drinking fructose leads to Metabolic Syndrome symptoms.

Soft drinks led to significant increase in abdominal fat, liver fat and blood triglycerides, higher BP.

Reducing fructose intake (28 to 10% calories) in children decreased weight, body fat, blood triglycerides and BP.

Higher consumption of sugary drinks correlated with increased aggression, both in humans and ants.

Mental disorders: high consumption of sugary drinks led to poorer performance in reading writing, grammar and maths in children.

The brains of Alzheimer’s sufferers had higher fructose concentrations (like 5-6-fold) than non-sufferers.

The survival switch reduces uptake of glucose by muscles and liver so that the brain has enough. It does this by blocking the effects of insulin.

Rats ingesting fructose lose their responsiveness to insulin in the memory and decision-making areas of the brain, so in effect fructose may be causing resistance to insulin also in the brain. This encourages exploration for food, but chronic stimulation can lead to brain damage, through reduction in ATP production. Neurons die without adequate ATP.

A Wider Issue

This book is one-eyed’, in the sense that it mainly discusses fructose and its many negative effects on our health. Dr Johnson does detour somewhat to a discussion of the contribution of different types of fat on our health. He starts by saying “Fructose is the criminal. Fat is only an accomplice.” Well, maybe. He uncritically repeats dogma about saturated fats and LDL-cholesterol. Then he cites evidence that omega-3 polyunsaturated fats tend to block or attenuate many of the effects of fructose. But he then claims that the literature on omega-6 fatty acids is mixed and inconclusive. His publication date was 1 March, 2022. The book Omega Balance, which is an exhaustive discussion about the role of the BALANCE between omega-3 and omega-6 fatty acids in human metabolism, was published on 1 January, 2023. Maybe he would have modified his comments if he had read Omega Balance before publication of his book. I have prepared a review of Omega Balance for the next Ebook.

Another diversion to dogma is found in his statement that red meats are distinctly harmful to our health. He says that ingestion of red meat can lead to the generation of toxic substances, such as TMAO (trimethylamine N-oxide). He states that we should stick with poultry, dairy and fish, but was apparently not aware that weight for weight, fish contribute much, much more TMAO (like several thousands of times more), than any red meat, and of course eating fish is good for us! Some 5 years ago, Chris Kresser concluded from a thorough search of the literature that there is no basis for concluding that TMAO is harmful to our health.

Despite these errors, I believe that Dr Johnson’s conclusions about fructose are soundly based on excellent scientific research.

Dr Johnson's Food Choices

👉 No sugary drinks. No artificial sweeteners: they encourage sugar consumption.

👉 Drink plenty of water.

👉 Eat breakfast, but no high glycaemic stuff.

👉 Fast for 16 h/d, or some other fasting regime such as 5/2 days.

👉 If you crave sugar, eat a small amount of whole fruit. The gut can process 4-5 g fructose at one intake, so limit fruit consumption to about this level at any one intake. No juices; no dried fruit; only small amounts of fresh. Figs are highest in fructose. Guidance: 1 apple (10 g fructose), 1 date (8), 1 cup blueberries (7.4), 1 banana (7), 1 nectarine (5), 1 plum (3), 1 cup raspberries (3).

👉 When you go on a diet and start losing weight, your body responds by reducing how much energy it uses. We need to increase energy production in mitochondria and minimise damage to mitochondria. Do this by blocking continuous activation of the survival switch, via a low fructose (20 g/d absolute maximum), low salt diet; start with a low carb/keto diet.

👉 Stimulate the repair of mitochondria and increase their number, by exercise: fast walking for 1 hour at a speed that you can just (with difficulty) continue to talk as you walk (about 4.4 km/h), several times a week.

👉 Eat dark chocolate (25 g/d) for its epicatechin content and drink green tea for its epigallocatechin. Both stimulate repair of mitochondria and the production of more of them.

 

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