The guide for doctors skeptical of low carb

Low-carb, high-fat (LCHF) nutrition saw a popular resurgence in 2018 as the ketogenic diet was the most “googled” diet of the year, and it retained that honor in 2019.1 Probably you’ve heard about it many times, including from patients.

Of course, low-carb eating isn’t new. The whole foods that compose a low-carb diet are similar to what humans have been eating for thousands of years. The recent popularity of low-carb diets, however, has come with a new scientific recognition of their health benefits.

Scientific studies of varying quality and duration show low-carb diets (generally less that 100 grams of carbohydrates per day) and ketogenic diets (less than 20-30 grams of carbohydrates per day) provide numerous health benefits including:

Unfortunately, no matter how popular they may be, and despite the numerous health benefits identified in the scientific literature, many people continue to think of low-carb and ketogenic diets as categorically unhealthy and dangerous.

Why is there such a disconnect? The answer may be due to a lack of familiarity with the science behind low-carb diets.

This guide explains the science and examines the misconceptions associated with low-carb diets. If you are a healthcare practitioner, we hope this guide will help you reconsider the risk-benefit balance of low-carb diets.

If you are not a healthcare practitioner, this guide may be able to prepare you for the most common concerns healthcare providers have. Your own experiences with a low-carb diet, plus this guide, can help your doctor better understand the potential benefits of a low-carb diet.

Below are evidence-based explanations that help sort fact from fiction:



Misconception 1: Nutritional ketosis is the same as ketoacidosis

Doctors likely never learned about nutritional ketosis in medical school or residency training. Instead, ketones are typically only mentioned as part of the life-threatening condition called ketoacidosis.

Ketoacidosis occurs mostly in people with type 1 diabetes and results from a deficiency of insulin and markedly elevated blood glucose levels. In this setting, ketone levels rise above 7 mmol/L (and usually above 10), causing the blood to become more acidic and placing the individual at tremendous risk.2

Ketoacidosis, however, is completely different from nutritional ketosis, where blood ketone levels usually range between 0.5-4 mmol/L and are accompanied by adequate insulin levels and low blood glucose.3 However, nutritional ketosis and ketoacidosis are physiologically very different, and the former has practically no health risk. This basic physiological difference is important for every helthcare practitioner to understand.4

Concerns about “ketosis” should not deter clinicians from recommending a low-carb or ketogenic lifestyle.5

Keto graph



Misconception 2: Low-carb diets may deliver short term weight loss, but at the cost of increased risk of heart disease or death

As low-carb eating has increased in popularity, paradoxically, there has also been a rise in studies claiming low-carb diets increase the risk of dying prematurely, or increase the risk for heart disease. While news headlines promote these studies, a closer look shows they do not reach meaningful conclusions and do not apply to well-formulated low-carb ways of eating.

For example, a 2013 review of 17 studies claimed there was a higher risk of death for those who ate less carbohydrate.6 How did these studies define “low carb”? This is a good question, as definitions varied among studies. Most studies used a “low-carbohydrate diet score,” based on carbohydrate percentage of total calories. They did not use absolute amounts of carbohydrate intake, which is how therapeutic low-carb diets are typically defined.7

Generally speaking, the lowest intake of carbohydrate in these studies averaged around 40% of calories.8 For a 2,000 calorie diet, 40% is 200 grams of carbs. While that is less than the standard American diet containing anywhere from 250-400 grams of carbs, it is far more than the 20 to 50 grams of daily carbs in low-carb and ketogenic diets used as interventions for obesity and chronic disease.

In addition, in most of the studies analyzed, there was no control for the quality of carbs. If a person is eating 200 grams of carbohydrates per day, there is plenty of room for refined and processed carbohydrate-containing foods. On a low-carb diet, carbohydrate calories come almost exclusively from vegetables and nuts, not from sugary, starchy, processed food. Few of the aforementioned studies controlled for the quality of carbohydrates, therefore the results are unlikely to apply to well-formulated low-carb or ketogenic diets.

These observational studies also suffer from healthy user bias.9 During the 1980s and 1990s, public health messages told us to avoid fat and consume more carbohydrate. The individuals who were eating 40% carbs and 40% fat in these studies — in other words, not following the dietary advice of the time — were also more likely to ignore other public health messages and to smoke, not exercise, and consume more calories. It is impossible for an observational study to account for all of these confounding variables, thus making the data far less useful.

Last, observational studies can only provide hypotheses; they do not show cause-effect relationships. They can suggest the need for better studies to be done to evaluate a potential association, but the low hazard ratios (less than 2.0) found in these studies are more likely to be a result of statistical noise than to reflect a true association.10

In conclusion, there are no moderate- or high-quality studies demonstrating that eating a whole-food, low-carb diet results in an increased risk of heart disease or early death.


Misconception 3: The amounts of fat allowed in a low-carb diet will raise LDL cholesterol levels

This turns out to not be true for the vast majority of individuals following a low-carb diet. Most studies show no significant change in low-density lipoprotein (LDL) cholesterol, but rather the potentially beneficial effects of raising HDL, lowering triglycerides, and reducing more atherogenic small, dense LDL particles.11 In fact, one study that looked at a 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculation for participants showed a decreased overall cardiovascular risk on a low-carb diet.12

There is a small subset of people, termed hyper-responders, whose LDL increases significantly on a LCHF diet. It is not known exactly how big this population is, but it is estimated to be around 5-25% of those who follow a low-carb diet.

Although we do not have outcome data in this specific population, we have to wonder if elevated LDL in the setting of a very low-carb diet is a unique mechanism that may have different outcome implications than elevated LDL for those following a low-fat diet or a more standard Western diet.

While studies have shown an association with increased risk in the latter situation, an increase in risk has not been investigated for those following a low-carb lifestyle. One thing that makes raised LDL from a low-carb diet unique is that it almost always occurs with a reduction of small dense LDL, an improvement of insulin resistance, decrease in blood pressure, increase in HDL, and decrease in triglycerides.13

This raises the question: For someone responding well to a low-carb diet, does elevated LDL have a conclusive pathological concern when other cumulative beneficial effects are present?

While this question has not been fully answered, it is important to look at a patient’s cardiovascular risk as a whole and interpret any lipid changes within the framework of the individual’s overall health profile. That does not mean LDL should be ignored by any means. Rather, LDL should be put into the broader context of overall health changes.14

In conclusion, LDL cholesterol does not increase in the majority of people on a LCHF diet. For those that do see an increase, this should be interpreted in the context of potential improvements in other cardiovascular risk factors. Until we have long term data, these cases may deserve a detailed, individual assessment rather than an automatic assumption of net harm or benefit. You can read more in our post about our official position on LDL cholesterol.

Fried eggs and bacon

Cholesterol and low-carb diets

GuideLearn what cholesterol is, how your body uses it, why low-carb and keto diets may lead to a change in blood cholesterol levels, and whether you should be concerned if your cholesterol increases with a keto or low-carb lifestyle.


Misconception 4: The excessive amounts of protein consumed on a low-carb diet can cause kidney damage, osteoporosis, and heart disease

This persistent myth is wrong on two counts. First, most low-carb diets are not high in protein. Most include about 20 to 30% of calories from protein, which can range from 70-150 grams of protein per day, well within normal recommended amounts of 10-35% of calories.15

There is no evidence to suggest that protein intake at this level is harmful to people with normal or even moderately decreased kidney function.16 If someone has severe kidney disease already, then a moderate-protein diet may be potentially harmful, so caution regarding a low-carb diet may be warranted in those cases.17 However, most LCHF and ketogenic diets are likely safe for all except those with pre-existing advanced renal failure.

In addition, protein consumption does not lead to compromised bone health.18 In fact, poor protein intake is more likely to contribute to bone loss.19 The concern that extra protein turns the blood more acidic thus harming our bones is an unfounded claim not supported by quality evidence as described in more detail here.

Finally, protein intake is not correlated with heart disease risk. As noted previously in the fat and heart disease section, data showing associations between protein intake and heart disease come from weak nutritional epidemiology studies that do not show causal relationships. Some studies, like the Nurses’ Health Study, demonstrate an inverse relationship between protein intake and risk of heart disease.20

Raw Beef Chicken and Fish Isolated Top View

Protein on a low-carb or keto diet

Guide Along with fat and carbohydrates, protein is one of the three macronutrients (“macros”) found in food, and it plays unique and important roles in the body. Here’s a guide to everything you need to know about protein on a low-carb or keto lifestyle.


Misconception 5: The meat and fat allowed on a low-carb diet increase the risk of cancer

For a detailed evaluation of fat intake and cancer risk, please see our guides on diet and cancer and saturated fats. In brief, the data linking fat to cancer risk is inconsistent, incomplete, and unreliable.

Observational trials that point to an increased risk of colorectal cancer from red meat suffer from the numerous weaknesses of all nutritional epidemiology studies of chronic disease.21 Importantly, a recent set of studies published in the Annals of Internal Medicine makes the case that available evidence from randomized controlled trials and observational studies does not support guidance to lower red meat intake to prevent cancer or heart disease.22

Despite the lack of evidence, the World Health Organization classified red meat as “probably” carcinogenic. However, the WHO relied almost exclusively on epidemiology studies and included only three randomized controlled trials in humans. This is a crucial point to make since randomized controlled trials, a much stronger level of evidence, show no association between red meat and cancer risk.23

In addition, the WHO also appeared to disregard other observational trials showing no association between meat and cancer.24 Thus the WHO evaluation is incomplete from a medical science standpoint, and the quality of the evidence does not support the strength of their conclusion. For more on the science behind concerns about red meat and cancer, see our evidence based red meat guide.

There is likewise a lack of association between fat intake and breast cancer. The Women’s Health Initiative (WHI), the largest randomized trial to address this issue, found no association between increased fat intake and increased risk of breast cancer.25 In addition, a meta-analysis of seven prospective studies including 337,000 women likewise showed no association between fat intake and breast cancer risk.26

In sum, the highest quality data do not suggests a causal relationship between fat intake and increased cancer risk.

Rendering of blood cells with one infected cell

Diet and cancer: What we know and what we don’t

Guide In this guide, we’ll look at what we know — and what we don’t know — about food and cancer.


Misconception 6: Whole grains are a necessary part of a healthy diet

To begin with, there is no nutritional requirement for carbohydrates.27

We cannot live without essential amino acids and essential fatty acids, but there is no such thing as an essential carbohydrate. Whole grains are not a requirement for survival. But have they been proven to promote health?

Studies demonstrate that whole grains are associated with better health when compared to refined grains.28 That is not much of a surprise given the lack of nutritional value and potential detrimental health effects of refined grains. However, there are no studies comparing whole grains to a grain-free diet composed of whole foods.

Evidence from the so-called Blue Zones, societies where individuals maintain good health into their 90s and 100s much more often than the general population, is also used to support the importance of whole grains. These communities frequently eat a high percentage of fiber and whole grains in their diet. We should recognize, however, that on average their caloric intake is two-thirds that of individuals in most industrialized nations, their food is predominately locally grown and prepared at home, they don’t eat fast food or processed foods, they are physically active their whole lives, and they have strong social connections.29

In addition, these findings aren’t based on studies of any kind, They are simply observations about populations whose lives are very different from contemporary industrialized societies. We cannot accurately extrapolate findings from those societies to countries where only 12% of the population may be considered metabolically healthy.

As a healthcare provider, determine if your patient is eating a diet high in refined grains. If they are, then switching to whole grains is likely beneficial. If not, then there is a lack of evidence supporting the health benefits of whole grains.

For more information, see our complete guide on whole grains.

Fibre Food for Healthy Eating

“Healthy” whole grains: What the evidence really shows

Guide Do whole grains live up to their reputation as a superfood? Let’s take a closer look at the very weak scientific evidence behind the claims made about their benefits.


Misconception 7: Low carb diets are deficient in fiber

Low-carb diets are not typically low in fiber. In fact, many low-carb and ketogenic diets contain nearly unrestricted amounts of above-ground vegetables such as broccoli, spinach, cauliflower, Brussels sprouts, green beans, bell peppers, zucchini, and more, all of which are high in fiber.

However, even if one chooses to eat a low-fiber, low-carb diet, there is no evidence that this is dangerous.30 As with whole grains, the majority of evidence in favor of fiber comes from comparing two different high-carbohydrate diets that are either high or low in fiber. Any high-carbohydrate diet that is low in fiber is more likely to contain highly processed and refined carbohydrates.

There is no question that higher-fiber, less-refined, less-processed carbohydrates are better than the lower-fiber, more-processed, more-refined carbohydrates.31 However, there is no evidence that fiber is a health requirement or that it is beneficial to add fiber to a low-carbohydrate diet composed of whole foods.

If a recommendation for more fiber leads to replacing unhealthy processed grains and carbs with whole, unprocessed grains, then more natural fiber is a step in the right direction. If, however, the aim is to add fiber to a diet already very low in carbohydrates, then we are operating outside the existing scientific knowledge without clear evidence for benefit.


Misconception 8: Fiber is required for a healthy gut microbiome

While it is true that our gut microbiome feeds on starchy fibers, we don’t know for certain that we need to feed them in this manner. For instance, our gut flora digest those starches into butyrate, a short chain fatty acid. Butyrate is structurally similar to betahydroxybutyrate (BHB), the main ketone body produced in nutritional ketosis.32

In addition, studies claiming low-carb diets negatively alter gut flora suffer from an inaccurate definition of low carb as 40% of calories, and include high amounts of industrial, rather than natural, fats. Since the studies also do not control for the quality of carbohydrates, they are impossible to extrapolate to a low-carb diet based on whole foods.33 The quality of carbohydrates is likely an essential factor, as microbiome health is dependent on the ratio of “good” and “bad” bacteria. Reducing refined carbohydrates, without any other interventions, likely helps reduce the “bad” bacteria, thus improving the ratio.34

Last, there is no convincing evidence that alterations in gut microbiome from a low-carb, high-fat diet have any implications for future health. Once again, the science is muddied by subjects eating a lower-quality diet, high in processed foods.

Scientists are in the early stages of gut microbiome research, and there is much we still do not know. More important than the microbiome is how a diet affects a person’s overall health. If someone significantly improves their health on a low-carb diet, we have to ask ourselves how important microbiome changes are.


Misconception 9: Low carb diets are too restrictive

This statement is all in the eye of the beholder. After all, doctors may recommend a vegan diet without the concern that it is too restrictive, despite the fact that it eliminates all animal products.

Does eating practically all the veggies, meat, cheese, eggs, poultry, fish, nuts, and seeds you want sound restrictive? For some, it might sound like heaven. Seeing that as a restrictive diet is a matter of opinion.

The job of healthcare practitioners is to find the right approach for each individual. Some may find a low-carbohydrate diet restrictive; some may find a vegan diet restrictive. Either way, that isn’t our decision to make.


Misconception 10: It is too difficult to maintain long term

Let’s be honest. Any meaningful lifestyle change has low compliance rates. Smoking cessation, regular exercise programs, even vegetarian diets have poor long-term compliance.35 However, if an intervention is a healthy approach for the individual, fear of compliance should not deter us from suggesting it. Instead, we should provide enough support to help someone maintain the change.

Despite the difficulty of long-term behavior change, some studies demonstrate excellent compliance with a ketogenic diet. The nonrandomized trial performed by Virta Health showed one- and two-year compliance rates of 83% and 74%.36 While this may not represent the general population as a whole, it shows that with good support, people who choose low-carbohydrate diets can thrive and maintain excellent compliance with them.

When we emphasize the importance of behavior change and improve our logistical support mechanisms for making that change happen, low-carb diets can play a meaningful role for many patients.


Misconception 11: Clinicians are required to follow guidelines that prescribe low-fat, low-calorie diets

The guidelines are changing. Low-carb diets are now recognized as an official treatment option by the American Diabetes Association (ADA) and The European Association for the Study of Diabetes (EASD).37 That makes low-carb diets an approved therapy.

In addition, there is a growing body of evidence in peer-reviewed journals to support that low-carb diets should be considered evidence-based care. Dr. David Unwin in the UK has published reports of his successes with low-carb nutrition and has impacted the guidelines given by the Royal College of General Practitioners.38 In addition, Virta Health has published their results using ketogenic diets to treat and reverse type 2 diabetes.39 In contrast, there are no published studies using the standard ADA diet to reverse diabetes as there are for low-carb diets.

There is now sufficient data and professional acceptance from the ADA to support the use of low-carb, higher-fat nutrition for the treatment of diabetes. That support can be extrapolated to pre-diabetes, insulin resistance, and metabolic syndrome with confidence that it is evidence-based care.

However, healthcare providers who are still hesitant can initiate a low-carb trial period of 6-months with a patient, with close follow-up of metabolic health markers such as waist circumference, blood pressure, HbA1c, HDL, triglycerides, fasting insulin, and other biomarkers. If these all improve, this should be sufficient evidence to support a patient’s decision. The key is recognizing that the evidence exists and knowing that a patient can be monitored for safety and efficacy.

Find a low-carb doctor

Misconception 12: A ketogenic diet will stunt a child’s growth

One of the first medical uses of a ketogenic diet was to help children with epilepsy to control their seizures. And it worked well. However, in order to get children to eat enough fat, most of these diets were based on synthetic shakes rather than real food. Unfortunately, that led to some rare complications of stunted growth and even reported deaths, presumably from nutrient or mineral deficiencies.40 There is no data to suggest similar concerns are warranted with a real food, ketogenic diet. However, when a ketogenic diet is used in children, careful attention should be paid to monitoring growth rate and including a variety of foods to supply adequate nutrients. When done in this manner, there is no evidence to suggest any potential harm.


Misconception 13: A low carb high fat diet is bad for the environment

This topic is much more complicated that it appears on the surface and is beyond the scope of this guide. Please see the three-part series on “The green keto meat eater” on the DietDoctor.com site or our podcast interview with Professor Frank Mitloehner. In short, there is more than one way to be environmentally friendly, and avoiding animal-sourced foods isn’t necessarily the best.


Conclusion

As physicians and healthcare providers, we all want what is best for our patients. On that, we can all agree.

One of the best ways we can help our patients is by helping them find a lifestyle they can maintain that improves their overall health.

But, how can we pretend there is one best diet for everyone? We are all individuals with varying degrees of metabolic health and different health goals. Thus, we all may need different diets to help us achieve those goals.

When it comes to lifestyle and nutrition, the challenge is finding the right approach for each individual.

At Diet Doctor, we support a low-carb, higher-fat way of eating because it has demonstrated tremendous benefits, and it has a growing body of evidence supporting those benefits. A low-carb diet may not be right for everyone, but it should be a consideration as there are many who will benefit from it.

This dietary intervention can not only improve the health of many patients, but — as many clinicians have found — it can help healthcare providers feel successful and satisfied in their work by helping patients feel empowered and in charge of their health.

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  1. As our post describes, intermittent fasting was the top trending diet, meaning it had the greatest increase from the prior year. But the keto diet remained the most overall searched for diet.

  2. American Family Physician 2013: Diabetic ketoacidosis: Evaluation and treatment [overview article; ungraded]

  3. There are rare reports of ketoacidosis in patients with type 2 diabetes who continue taking SGLT-2 inhibitors (diabetes medicines under the trade names Jardiance, Invokana, and others) after beginning a low-carb diet. In this setting, glucose levels may continue to be normal and the condition is therefore called euglycemic ketoacidosis

    Journal of Diabetes Investigation 2015: Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet [case report; very weak evidence]

  4. Nutrition Bulletin 2011: Ketosis, ketoacidosis and very-low-calorie diets: Putting the record straight [overview article; ungraded]

  5. Many clinicians are even using low-carb diets to treat patients with type 1 diabetes. You can learn more about this from our evidence based guide, as well as from our podcast interviews with Dr. Jake Kushner and Dr. Ian Lake.

  6. PLoS One 2013: Low-carbohydrate diets and all-cause mortality: a systematic review and meta-analysis of observational studies [observational/epidemiological data; very weak evidence]

  7. Nutrition and Metabolism 2008: Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: Time for a critical
    appraisal
    [review; ungraded]

    Diabetes Management 2019: A clinician’s guide to inpatient low carbohydrate diets for remission of type 2 diabetes: Toward a standard of care protocol [case study; very weak evidence]

  8. The 2013 study was not the only one to define “low-carb” as less than 40% of calories. A 2020 publication from the Harvard Scool of Public Health used the same improper definition to conclude low-carb diets are dangerous. We reviewed this study in more detail in a prior post.

  9. Journal of General Internal Medicine 2011: Healthy user and related biases in observational studies of preventive interventions: a primer for physicians [overview article; ungraded]

  10. While a cut off value of 2 is not universally agreed upon, it is included as part of the GRADE criteria for analyzing study quality.

    In addition, the concept of needing a large enough difference for a meaningful finding is also supported by the following references:

    Advances in Nutrition 2018: Limiting dependence on nonrandomized studies and improving randomized trials in human nutrition research: why and how

    JAMA 2018: The challenge of reforming nutritional epidemiologic research

    PLoS Medicine 2005: Why most published research findings are false

    The Lancet 2019: Real-world studies no substitute for RCTs in establishing efficacy

    Frontiers in Nutrition 2018: The failure to measure dietary intake engendered a fictional discourse on diet-disease relations

  11. Nutrition in Clinical Practice 2011: Low-carbohydrate diet review: shifting the paradigm [overview article; ungraded]

    Annals of Internal Medicine 2010: Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet
    A randomized trial
    [moderate evidence]

  12. Cardiovascular Diabetology 2018: Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study [non-randomized trial; weak evidence]

  13. Lipids 2009: Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet [randomized trial; moderate evidence]

    Obesity Reviews 2012: Systematic review and meta-analysis of clinical trial of the effects of low carbohydrate diets on cardiovascular risk factors [systematic review of clinical trials; strong evidence]

  14. The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines state any LDL above 190 mg/dL needs to be treated with a statin and a low-fat diet. However, the evidence behind that recommendation did not include the subset of individuals following a well-formulated, LCHF diet and did not consider other health benefits that may coincide with the LDL elevation.

  15. At Diet Doctor, we recommend most people aim for a protein range of 1.2-2.0g/kg/day as we detail in our guide on protein intake.

  16. You can read more about this topic in our dedicated guide on low-carb diets and kidney health. Below are supportive references.

    Journal of the American Dietetic Association 2010: Renal function following long-term weight loss in individuals with abdominal obesity on a very-low-carbohydrate diet vs. high-carbohydrate diet [randomized trial; moderate evidence]

    The Journal of Nutrition 2018: Changes in kidney function do not differ between healthy adults consuming higher- compared with lower- or normal-protein diets: A systematic review and meta-analysis [strong evidence]

  17. American Journal of Kidney Disease 1996: Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study [randomized trial; moderate evidence]

  18. Nutrition 2016: Long-term effects of a very very-low-carbohydrate weight-loss diet and an isocaloric low-fat diet on bone health in obese adults [randomized trial; moderate evidence]

  19. International Journal for Vitamin and Nutrition Research 2011: Protein intake and bone health [overview article; ungraded]

  20. American Journal of Clinical Nutrition 1999: Dietary protein and risk of ischemic heart disease in women [observational study; very weak evidence]

  21. Oncotarget 2017: Red and processed meat consumption and colorectal cancer risk: a systematic review and meta-analysis [observational study; very weak evidence]

  22. Annals of Internal Medicine 2019: Effect of lower versus higher red meat intake on cardiometabolic and cancer outcomes: A systematic review of randomized trials [strong evidence]

    Annals of Internal Medicine 2019: Patterns of red and processed meat consumption and risk for cardiometabolic and cancer outcomes: A systematic review and meta-analysis of cohort studies [observational/epidemiological data; very weak evidence]

  23. Cancer Epidemiology, Biomarkers & Prevention 2007: The Polyp Prevention Trial–continued follow-up study: no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization [randomized trial; moderate evidence]

  24. Nutrition Journal 2015: A review and meta-analysis of prospective studies of red and processed meat, meat cooking methods, heme iron, heterocyclic amines and prostate cancer [observational study; very weak evidence]


  25. Journal of the American Medical Association 2006: Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial
    [randomized trial; moderate evidence]

  26. New England Journal of Medicine 1996: Cohort studies of fat intake and the risk of breast cancer — a pooled analysis [observational study; very weak evidence]

  27. BMJ 2018: Dietary carbohydrates: role of quality and quantity in chronic disease [overview article; ungraded]

    There is a misconception that the brain requires carbohydrates. This is untrue. The brain requires glucose, but that is very different from saying the brain requires carbohydrates. We explore this topic in more detail in our evidence-based guide.

  28. American Journal of Clinical Nutrition 2017: Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women [moderate evidence]

    American Journal of Clinical Nutrition 2018: The effects of whole-grain compared with refined wheat, rice, and rye on the postprandial blood glucose response: a systematic review and meta-analysis of randomized controlled trials [strong evidence]

  29. The following retrospective analysis showed chronic caloric reduction practiced by Okinawans.

    Annals of the New York Academy of Science 2007: Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span [nonrandomized study, weak evidence]

    Other lifestyle practices are detailed in The Blue Zones book. This is a detailed depiction of the author’s observation of their lifestyles, but it is not scientific research.

  30. World Journal of Gastroenterology 2007: Fiber and colorectal diseases: separating fact from fiction [overview; ungraded]

  31. Nutrition Review 2009: Health benefits of dietary fiber. [review study; weak evidence]

  32. Environmental Microbiology 2017: Formation of propionate and butyrate by the human colonic microbiota [overview of mechanism; ungraded]

    Nature 2019: Prominent action of butyrate over betahydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule [overview of mechanism; ungraded]

  33. Gut 2019: Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial [randomized trial; moderate evidence]

  34. The society believed to have the “healthiest” and most diverse gut bacteria are the Hadza, a hunter-gatherer society that has no exposure to processed or refined carbohydrates. However, this is observational and other potential explanations could exist.
    Science 2017: Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania[observational study; very weak evidence]

  35. American Journal of Lifestyle Medicine 2016: Long-term adherence to health behavior change [overview article; ungraded]

  36. Diabetes Therapy 2018: Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study [non-randomized trial; weak evidence]

    Frontiers in Endocrinology 2019: Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: A 2-year non-randomized clinical trial [weak evidence]

  37. Diabetes Care 2018: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

  38. Practical Diabetes 2014: Low carbohydrate diet to achieve weight loss and improve HbA1c in type 2 diabetes and pre‐diabetes: experience from one general practice [case study/series; weak evidence]

    The BMJ 2015: A patient request for some “deprescribing” [case study; weak evidence]

  39. Diabetes Therapy 2018: Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study [non-randomized trial; weak evidence]

  40. Developmental Medicine and Child Neurology 2002: Growth of children on the ketogenic diet [observational study; very weak evidence]

    Epilepsia 2003: Selenium deficiency associated with cardiomyopathy: a complication of the ketogenic diet [case report; very weak evidence]