50 years ago, the sugar industry formed a Sugar Research Foundation (SRF) and paid scientists to write a paper. The paper downplayed the effects of sugar on heart disease and demonised fat instead. This paper formed the basis of the first US nutritional guidelines, which were then copied across the world. Here's an article describing more.
Despite no evidence of this being true, aside from that review funded by the SRF, and the majority of studies pointing to fat being healthy, these guidelines stuck and so carbohydrates have been steadily replacing fat over the last 50 years. Sugar levels are now a global epidemic. The current levels of diabetes and obesity are the highest ever, both having doubled since 1980.
Fundamentally of course it is true that energy is always conserved. However, when translating that to "calories-in calories-out" in the way we usually see it, there are two huge factors which are almost always forgotten. Firstly, the fraction of the calories actually go "in"; and secondly all the different ways, aside from exercise, that calories come "out". These both make a huge difference to the calories in/calories out balance, before we even start talking about how food impacts your hormones and cravings.
Calories-In: The idea of standardised calorie content of food is very misleading. In fact - despite the seeming accuracy of the values - food producers have a very hard time estimating it. They are calculated based on macros - as an average for fat, protein and carbs. This oversimplification doesn't take into account how different types of carbs are digested to different degrees, nor how different people can get more or less energy from same food. This results in calorie content on packaging having errors of over 30% in the case of nuts and up to 25% error in common snacks.
This isn't to say there's anything nefarious about it. The calories you manage to take from a food depends on your unique microbiome and how it processes the food. When people absorb difference amount of energy from foods, then the true calories consumed are very different to what the average value is. An incredible example of this is how some people's gut manages to get energy out of Diet Coke - which on the packaging, and for most people, has no calories. [More details in section on Microbiome]
Calories-Out: It's not just by doing exercise that you burn calories, 60-75% of daily calorie expenditure calories come out through your Basal Metabolic Rate (how many calories you use at rest). This energy all ultimately turns to heat and is called thermogenesis. Increasing your BMR (ie speed of the metabolism) has a huge impact on your "calories-out", even without doing any more exercise. Restricting calories can reduce your BMR, as your body learns to adapt to less calories. There are arguments both for and against having a lower BMR, but in any case, it highlights how "calories out" is much more than just about moving more/less. [More details in section on Metabolic Pathways]
To understand the internal workings of our body, we look at the metabolic pathways. This is the ways in which our body metabolises food - here is a useful (and surprisingly one of the simplest!) description and diagram of metabolic pathways. In the modern day diet, which is rich in carbs and sugar, your body is mainly using the glucose pathway. This pathway is regulated by two main hormones: insulin and ghrelin. Understanding these hormones helps explain the problem of spiking and crashing sugar levels.
Insulin: Insulin shifts glucose into your fat cells. When you eat carbohydrates your body breaks them down to glucose, which is the shortest chain carbohydrate. This causes your sugar levels spike. Insulin is then produced, to push sugar out of your bloodstream and into your cells. This means that higher insulin levels cause weight gain (even if your "calories in" and "calories out" are exactly the same). At higher insulin levels, your body gets more efficient at moving glucose into fat cells. This was shown in the study: Insulin increases body fat despite control of food intake and physical activity. In this study they fed mice exactly the same food and same exercise levels, but injected one group with insulin. Despite having exactly the same "calories in" and "calories out" the mice with higher insulin got a lot fatter.
Ghrelin: Ghrelin makes you hungry and conserves energy. Ghrelin is named the "hunger hormone" because of its role of dealing with sugar levels crashes. Ghrelin is used to stop your sugar levels going too low, so causes you hunger and cravings, and also saves energy by decreasing heat expenditure in your body. This study explains ghrelin in more detail: Ghrelin: much more than a hunger hormone. The type of food really impacts the amount of ghrelin produced. This study shows how high fat meals reduce ghrelin for 6 hours, meaning "feeling full" for 6 hours, but high carbohydrate meals reduce ghrelin only for 3 hours, then increase it much higher than it was before eating, causing hunger again by 3 hours time. See Fig2.D in this paper: A high carbohydrate, but not fat or protein meal attenuates postprandial ghrelin, PYY and GLP-1 responses in Chinese men.
Why are these hormones so sensitive? Because we only need glucose when doing intense physical exercise, we only keep a maximum of around 2,000 kcals of glucose in reserve in our "glycogen stores". Fat on the other hand, stores 3,500 kcals per pound. So if we have even just 28 lbs (13 kg) of excess fat on us, then that's 100,000 kcals - or 50 times as much energy stored in fat as in glucose. This could explain why these hormones can be affected by just one carb rich meal.
An Alternative Pathway: The alternative to using the glucose pathway, spiking insulin and ghrelin, and causing cyclical hunger pangs, is to eat a high fat diet and use another pathway, ketones. This pathway converts fat into ketones which become a source of energy. It converts fat from your fat cells along with fat from food, and can easily switch between the two (meaning no spikes in hormones). Rather than needing hormones to regulate this pathway, it can easily switch sources from the fat you eat, to the fat cells in your body - not needing to switch any directions.
Low carb diets (eg keto, paleo or Atkins) can resolve the problem of high glucose, insulin and ghrelin levels by switching away from the carb/glucose pathway to the fat/ketone pathway. However there have been some concerns about low carb diets being "extreme" or having too much saturated fat. Let's address these concerns by looking at the research, particularly the summaries and meta-analyses collating results from multiple studies, so we are not biasing ourselves.
Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. This is a huge meta-analysis of low carb vs low fat diets. They found that low carb diets had higher weight loss (2.17 kg more on average). Also they found that on low carb diets the cholesterol ratio (now recognised to be the most useful cholesterol metric) improved.
Healthline: 23 Studies on Low-Carb and Low-Fat Diets. This is a great summary of 23 studies which compared low fat vs low carb diets. Weight loss was greater in 20 out of 21 of the studies which looked at weight loss. The markers for cardiovascular risk, such as triglycerides and cholesterol ratio, were improved in all the studies that measured them. The graphics at the end of that article are particularly interesting and help to compare the outcomes.
Diet Doctor: The science of low carb. Here is another article that not just shows the weight loss benefits of low carb, but also looks into studies on health benefits and addresses the concerns that some people have.
Healthline: 5 Studies on Saturated Fat deals with debunking the myth that saturated fats (found in meat, dairy products and coconut oil) are bad for you. Researchers have found no link between saturated fat and heart disease/stroke/diabetes, only that increasing your polyunsaturated or monounsaturated fat intake may in fact reduce your risk!
Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. This large meta-analysis has found no link between saturated fat and heart disease.
NY Times: Study Questions Fat and Heart Disease Link also talks about it.
However, one missing piece in these studies, and low carb diets in general, is the acceptance that food affects different people in different ways. This may be due to genetics, gut microbiome or other factors, and is a hot area of research right now with many researchers trying to figure out the main cause.
Especially interesting is how people have unique glucose responses to different foods. This will mean that some people can eat specific carbs without having a glucose spike at all. An excellent study showing this effects is: Personalized Nutrition by Prediction of Glycemic Responses. For example, Figure 2G shows an example of how two people could have completely opposite responses to cookies and bananas. One person got spiked by cookies but not bananas, and the other got spiked by bananas but not cookies!
These researchers explore the idea that the differences in response are caused by your unique gut microbiome. Your gut microbiome refers to the the trillions of bacteria living in your gut. When you are born, you take the microbiome of your mother and then over the years it develops with food you eat and your environment. In fact it is always developing, so if you take a strong course of antibiotics you'll kill a portion of it, and if you eat totally new foods you'll expand the diversity of it. It impacts many things including weight gain, what foods suit you, allergies, insulin sensitivity and potentially many more aspects of your life. There's a lot of interesting research right now on how it impacts your mental health too. Here's an article from the BBC on that idea: How bacteria are changing your mood.
Aside from weight gain and sugar crashes, researchers are finding many other problems with spiking sugar levels. Some of these are: insulin resistance (and then diabetes), heart disease, dementia and cancer. There are issues with both high average sugar levels and post meal sugar spikes. This is true for both diabetics and non-diabetics. We'll focus here mostly on non-diabetics, because no doubt diabetics already know the value of keeping their sugar levels balanced!
Insulin Resistance: High sugar levels have been shown to cause beta cell damage, which causes higher insulin resistance and may lead to diabetes. There are many studies showing associations, but these two studies explicitly show high sugar levels causing beta cell damage. This one shows that keeping sugar levels over 150 mg/dl (8.3 mmol/L) caused beta cell damage in mice: β-Cell Death and Mass in Syngeneically Transplanted Islets Exposed to Short- and Long-Term Hyperglycemia. And this one shows that sugar levels above 140mg/dl (7.8mmol/L) caused beta cell damage in humans: Determinants of glucose toxicity and its reversibility in the pancreatic islet β-cell line, HIT-T15
So the more you spike your sugar levels, the more resistant to insulin you become. Making it even more difficult for your body to lower your sugar levels, causing even more cell damage, more insulin resistance, then diabetes - where even 2 hours after the meal your sugar levels could still be above 7.8mmol/L (140mg/dl).
Heart Disease: Many studies have shown a link between high sugar levels and cardiovascular disease (CVD). They find this to be true in both diabetics and non-diabetics. Particularly interesting are the studies that show post-meal spikes (not just average or fasting sugar level) are the key indicator.
This study found that spiking glucose over 155 mg/dl(8.6 mmol/L) after a meal increased markers for CVD (subclinical inflammation, high lipid ratios and insulin resistance). “Therefore, 1hPG [1 hour post-meal glucose]>155 mg/dl could be considered a new 'marker' for cardiovascular risk.” Inflammation markers and metabolic characteristics of subjects with one-hour plasma glucose levels. 8.6 mmol/L may sound high - but every person we've seen data for has had at least 1 meal which spikes them over this level (main culprits were: cereal, pizza, coke). Here's another study linking the height of the post meal spikes and heart disease, in non-diabetics: Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women.
These studies focus on average sugar levels, and their link with coronary heart disease/CVD in both people with and without diabetes shown here: Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. and here: Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk.. This study shows average blood sugar level is more predictive than fasting blood sugar: Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults.
Dementia: This study shows that higher glucose levels may be a risk factor for dementia: Glucose Levels and Risk of Dementia. This study shows higher glucose levels associated with neurodegeneration and ageing, even in people without diabetes: Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study.
Cancer: The fact that cancer mainly grows using sugar (glucose and fructose) has been well known and studied for years - it's known as the Warburg Effect. There are many studies on this process, but it seems useful to also look at the link between high sugar in people and their risk of cancer: Prospective Study of Hyperglycemia and Cancer Risk. Also these studies show that once cancer develops, how the growth and progression can be managed by switching from glucose to ketone metabolism: Cancer as a Metabolic Disease, Pilot cancer patients and keto diet and Keto diet as adjuvent cancer therapy.
If you want to learn more, there are some great doctors, writers and film-makers already dedicated to explaining and summarising the science behind sugar levels. Here are some of our favourites. If you come across anything else interesting let us know at firstname.lastname@example.org
Burn Fat Not Sugar written by Dr Ted Naiman, a family medicine physician, writer and YouTube star.
Health Hackers podcast - by Gemma Evans, there's some really good diet articles on her site too
the Drive - by Peter Attia, for more insights into health optimisation for longevity and quality of life
The Magic Pill. This is an excellent documentary exploring sugar and in particular the Paleo diet. They explore natural and historical elements of food production. The science is also explored - they reference papers and have some case studies - switching people with Epilepsy, Asthma, Obesity, Cancer and Diabetes onto Paleo diet.
This video is particularly good at summarising the science of sugar levels. It is also by Dr Ted Naiman, of the blog mentioned above.