Low Carb Science

Here is a collection of research articles from scientific journals, pertaining to low carb and high fat diets. They are grouped by topic in the Table of Contents below.

For each article, I’ve included a short summary of its main findings. You can navigate to the individual article by clicking on the underlined link below each citation.

These studies show that a diet low in carbs and high in fat, like the ketogenic diet, is effective for treating obesity, insulin resistance, diabetes, and other metabolic conditions. Meal frequency and timing can be important — high meal frequency (like snacking or grazing) increases weight and reduces satiety, whereas fasting between meals or skipping meals is beneficial for keeping insulin low.

Diabetes

Skytte et al., “Effects of carbohydrate restriction on postprandial glucose metabolism, beta-cell function, gut hormone secretion, and satiety in patients with type 2 diabetes,” Am J Physiol Endocrinol Metab, Oct. 2020.
doi: 10.1152/ajpendo.00165.2020

In a cross-over randomized trial, 28 type 2 diabetics underwent 6 weeks of a low carb diet and 6 weeks of a conventional diabetes diet. The low carb diet reduced glucose excursions (postprandial glucose area under curve by 60%, 24h glucose by 13%), increased subjective satiety by 18%, and improved beta-cell function.

Chen et al., “Effect of a 90 g/day low-carbohydrate diet on glycaemic control, small, dense low-density lipoprotein and carotid intima-media thickness in type 2 diabetic patients: An 18-month randomised controlled trial,” PLOS ONE, vol. 15, no. 10, p. e0240158, Oct. 2020.
doi: 10.1371/journal.pone.0240158

In a randomized controlled trial of 85 type 2 diabetics over 18 months, patients on a low carb diet (90 g/d) had better glycemic control, lowered blood pressure, and decreased weight/waist/hip circumference compared to the control group. There were no adverse effects on lipid profiles.

Athinarayanan et al., “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,” Front. Endocrinol., vol. 10, 2019.
doi: 10.3389/fendo.2019.00348

In a 2-year study of type 2 diabetics, participants selected either a low carb diet (initially <30 g total carbs daily) or standard diabetes care. In the group with a low carb diet, diabetes resolution occurred for half of them. The group with standard care did not experience diabetes resolution or improvement, and some participants worsened.

Huntriss et al., “The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials,” European Journal of Clinical Nutrition, vol. 72, no. 3, pp. 311–325, Mar. 2018.
doi: 10.1038/s41430-017-0019-4

From analyzing 18 randomized control trials of interventions for type 2 diabetic adults, the low carb diet resulted in favorable outcomes for HbA1c, triglycerides, and HDL cholesterol. It also reduced requirements for diabetes medication.

Bhanpuri et al., “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,” Cardiovasc Diabetol, vol. 17, no. 1, p. 56, 01 2018.
doi: 10.1186/s12933-018-0698-8

In a non-randomized controlled trial of type 2 diabetic patients, 262 were assigned to a ketogenic intervention and they improved most biomarkers of cardiovascular risk after 1 year.

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Weight Loss

Dashti et al., “Long-term effects of a ketogenic diet in obese patients,” Exp Clin Cardiol, vol. 9, no. 3, pp. 200–205, 2004.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/

Obese patients were subjected to a 24-week ketogenic diet. After the study, patients had significantly decreased weight and body mass index, decreased total cholesterol, increased HDL cholesterol, decreased LDL cholesterol, decreased triglycerides, and decreased blood glucose. There were no significant side effects.

Foster et al., “Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial,” Annals of Internal Medicine, vol. 153, no. 3, pp. 147–157, Aug. 2010.
doi: 10.7326/0003-4819-153-3-201008030-00005

Patients were treated with a low fat or low carb diet for 2 years. Both diets were effective for weight loss, but the low carb patients had more favorable changes in cardiovascular disease risk factors.

Bueno et al., “Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials,” British Journal of Nutrition, vol. 110, no. 7, pp. 1178–1187, Oct. 2013.
doi: 10.1017/S0007114513000548

From an analysis of randomized controlled trials (up to 2012, with at least 1 year of follow-up), they found that a keto diet achieved a greater weight loss than a low-fat diet in the long term.

Gibas and Gibas, “Induced and controlled dietary ketosis as a regulator of obesity and metabolic syndrome pathologies,” Diabetes & Metabolic Syndrome, vol. 11 Suppl 1, pp. S385–S390, Nov. 2017.
doi: 10.1016/j.dsx.2017.03.022

From a study of 30 adults diagnosed with metabolic syndrome over 10 weeks, a keto diet with no exercise out-performs a standard American diet with exercise in terms of weight, body fat percentage, BMI, and hemoglobin A1c.

Hyde et al., “Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss,” JCI Insight, vol. 4, no. 12, Jun. 2019.
doi: 10.1172/jci.insight.128308

Obese participants diagnosed with metabolic syndrome were given low/med/high carb diets. After 4 weeks, a low carb diet was found to be most effective at reversing metabolic syndrome.

Goss et al., “Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial,” Nutrition & Metabolism, vol. 17, no. 1, p. 64, Aug. 2020.
doi: 10.1186/s12986-020-00481-9

In a 8-week randomized trial of 34 obese men and women (age 60-75), participants lost an average of 9.7% total fat on a very low carb diet and 2.0% on a low fat diet. The very low carb group experienced 3 times greater loss in visceral adipose tissue compared to the low fat group.

Choi et al., “Impact of a Ketogenic Diet on Metabolic Parameters in Patients with Obesity or Overweight and with or without Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials,” Nutrients, vol. 12, no. 7, p. 2005, Jul. 2020.
doi: 10.3390/nu12072005

From studying 14 randomized control trials using the keto diet for metabolic control for overweight patients, they found that the keto diet resulted in greater glycemic control, substantial weight reduction, and improved lipid profiles compared to low fat diets.

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Brain

Mujica-Parodi et al., “Diet modulates brain network stability, a biomarker for brain aging, in young adults,” PNAS, vol. 117, no. 11, pp. 6170–6177, Mar. 2020.
doi: 10.1073/pnas.1913042117

From neuroimaging datasets, brain aging correlates with poorer cognition and accelerates with insulin resistance. Ketones increase the stability of brain networks, whereas glucose destabilizes them. The aging brain may be protected by ketone utilization because it increases the energy available to the brain.

Cunnane et al., “Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing,” Nature Reviews Drug Discovery, vol. 19, no. 9, pp. 609–633, Sep. 2020.
doi: 10.1038/s41573-020-0072-x

In age-related neurodegenerative disorders like Alzheimer and Parkinson disease, sufficient energy is not being provided to the brain through glucose metabolism. Ongoing clinical trials show that a ketogenic intervention improves cognitive function.

El-Rashidy et al., “Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study,” Metabolic Brain Disease, vol. 32, no. 6, pp. 1935–1941, 2017.
doi: 10.1007/s11011-017-0088-z

Autistic children received either a keto diet, a gluten-free dairy-free diet, or a balanced nutrition diet (control group). After 6 months, both diet groups showed significant improvement in autism rating scales and evaluation tests, with the keto group scoring better in cognition and sociability than the gluten-free dairy-free group.

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Cancer

Zhang et al., “Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer,” J. Agric. Food Chem., Aug. 2020.
doi: 10.1021/acs.jafc.0c04041

From studying mice, results indicate that a keto diet can prevent the progression of colon tumor via oxidative stress.

Khodabakhshi et al., “Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study,” Nutrition and Cancer, vol. 72, no. 4, pp. 627–634, May 2020.
doi: 10.1080/01635581.2019.1650942

In a randomized controlled trial of 60 breast cancer patients, half were assigned a keto diet and the other half was a control group with a standard diet. After 3 months, 100% of the keto group survived compared to 60% of the control group.

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Exercise

Murphy et al., “High-Fat Ketogenic Diets and Physical Performance: A Systematic Review,” Adv Nutr, 2020.
doi: 10.1093/advances/nmaa101

From a review of previous randomized and non-randomized studies, the keto diet does not appear to have a positive or negative impact on physical performance compared to mixed macronutrient diets. However, conflicting results between studies may be attributed to diet duration, training status, performance test, and sex differences.

Miller et al., “A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health,” American Journal of Physiology-Endocrinology and Metabolism, Sep. 2020.
doi: 10.1152/ajpendo.00305.2020

Twenty-nine active adults completed a 12-week exercise program after self-selecting into a ketogenic diet or maintaining of their habitual diet. The keto group had decreased fasting insulin, insulin resistance, and visceral fat. By isolating mitochondria from muscle, researchers looked at mitochondrial function and found that the keto group had increased ATP production (36%).

Gregory, “A Low-Carbohydrate Ketogenic Diet Combined with 6-Weeks of Crossfit Training Improves Body Composition and Performance,” Int J Sports Exerc Med, 2017.
doi: 10.23937/2469-5718/1510054

Subjects following a low carb ketogenic diet and CrossFit training saw decreases in their body fat percentage, fat mass, and BMI while maintaining their lean body mass. They also had improvements in their performance power and time.

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Sucrose (Sugar)

Mantantzis et al., “Sugar rush or sugar crash? A meta-analysis of carbohydrate effects on mood,” Neuroscience & Biobehavioral Reviews, vol. 101, pp. 45–67, Jun. 2019.
doi: 10.1016/j.neubiorev.2019.03.016

From a systematic review and meta analysis investigating the relationship between carb ingestion and mood, carbs lower alertness within 1 hour of consumption and increase fatigue within 30 minutes of consumption.

Ginieis et al., “The ‘sweet’ effect: Comparative assessments of dietary sugars on cognitive performance,” Physiology & Behavior, vol. 184, pp. 242–247, Feb. 2018.
doi: 10.1016/j.physbeh.2017.12.010

A double-blind, placebo-controlled study of 49 people showed that consuming sucrose (sugar) and glucose leads to poorer performance on cognitive tasks such as simple response time and arithmetic, compared to fructose or a control (sucralose). This effect is especially pronounced in the fasted state.

DiNicolantonio and O’Keefe, “Markedly increased intake of refined carbohydrates and sugar is associated with the rise of coronary heart disease and diabetes among the Alaskan Inuit,” Open Heart, vol. 4, no. 2, p. e000673, Nov. 2017.
doi: 10.1136/openhrt-2017-000673

Analysis of the Alaskan Inuit diet showed that higher consumption of carbs and sugar is linked to the rise of coronary heart disease and diabetes.

Grasgruber et al., “Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries,” Food & Nutrition Research, vol. 60, no. 1, p. 31694, Jan. 2016.
doi: 10.3402/fnr.v60.31694

From a study of relationships between nutritional factors and the prevalence of cardiovascular diseases in Europe, the major correlate of high cardiovascular disease risk was the proportion of dietary energy from carbs and alcohol.

Gardener et al., “Diet soft drink consumption is associated with an increased risk of vascular events in the Northern Manhattan Study,” Journal of General Internal Medicine, vol. 27, no. 9, pp. 1120–1126, Sep. 2012.
doi: 10.1007/s11606-011-1968-2

Daily consumption of diet soft drinks are linked to an increased risk for stroke and other vascular events.

Dhingra et al., “Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community,” Circulation, vol. 116, no. 5, pp. 480–488, Jul. 2007.
doi: 10.1161/CIRCULATIONAHA.107.689935

Among middle aged adults, soft drink consumption is associated with higher incidence of cardiometabolic risk factors.

Schulze et al., “Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women,” JAMA, vol. 292, no. 8, pp. 927–934, Aug. 2004.
doi: 10.1001/jama.292.8.927

Sugary beverages are linked to weight gain and increase in type 2 diabetes in women.

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Fructose

Stanhope et al., “Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women,” The Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 10, pp. E1596-1605, Oct. 2011.
doi: 10.1210/jc.2011-1251

Among 48 adults, consumption of fructose at 25% of energy requirements for 2 weeks increased cardiovascular factors such as triglycerides, low-density lipoprotein concentration (LDL), and apolipoprotein B concentration (apoB) more than glucose consumption.

Beck-Nielsen et al., “Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects,” The American Journal of Clinical Nutrition, vol. 33, no. 2, pp. 273–278, Feb. 1980.
doi: 10.1093/ajcn/33.2.273

Young healthy subjects consumed their usual diets plus either glucose or fructose. After one week, the group with fructose feeding had a significant reduction in their insulin binding and insulin sensitivity, whereas the glucose group had no significant change. Fructose, rather than glucose, appears responsible for the insulin binding/sensitivity issue in sucrose.

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Number Of Meals

Cameron et al., “Increased meal frequency does not promote greater weight loss in subjects who were prescribed an 8-week equi-energetic energy-restricted diet,” The British Journal of Nutrition, vol. 103, no. 8, pp. 1098–1101, Apr. 2010.
doi: 10.1017/S0007114509992984

In a randomized trial of 16 obese adults eating the same dietary energy restriction, those who ate a higher meal frequency did not experience greater weight loss than those with a lower meal frequency.

Leidy et al., “The influence of higher protein intake and greater eating frequency on appetite control in overweight and obese men,” Obesity (Silver Spring, Md.), vol. 18, no. 9, pp. 1725–1732, Sep. 2010.
doi: 10.1038/oby.2010.45

In a study of obese men, satiety and fullness-related responses were greater on a higher protein diet but lower when they increased their eating frequency. This challenges the idea that increasing the number of eating occasions increases satiety.

Koopman et al., “Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial,” Hepatology (Baltimore, Md.), vol. 60, no. 2, pp. 545–553, Aug. 2014.
doi: 10.1002/hep.27149

In a 6-week randomized control trial of 36 lean healthy men, high meal frequency increases abdominal fat, but increasing meal size does not, which suggests that frequent snacking can lead to obesity.

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Time Of Day

Madjd et al., “Effects of consuming later evening meal versus earlier evening meal on weight loss during a Weight Loss Diet: a randomized clinical trial,” British Journal of Nutrition, pp. 1–25, 2020.
doi: 10.1017/S0007114520004456

Overweight women were randomly assigned to a 7:00-7:30 PM or 10:30-11:00 PM meal group for 12 weeks. Those assigned to the earlier meal had a greater reduction in weight, waist circumference, total cholesterol, triglycerides, and insulin.

Sievert et al., “Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomised controlled trials,” BMJ, vol. 364, Jan. 2019.
doi: 10.1136/bmj.l42

In this systematic review of 13 randomized control trials published between 1990 and 2018, total daily energy intake for breakfast eaters was 260 kcal higher. Weight loss was slightly in favor of people who skipped breakfast.

Betts et al., “The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults,” The American Journal of Clinical Nutrition, vol. 100, no. 2, pp. 539–547, Aug. 2014.
doi: 10.3945/ajcn.114.083402

In a 6-week randomized control trial, obese adults either ate breakfast by 11 AM or fasted until noon. Contrary to popular belief, eating breakfast does not affect resting metabolism (resting metabolic rate stable within 11 kcal/d). Breakfast eaters averaged 539 extra calories per day compared to those that skipped breakfast.

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Fasting

Cienfuegos et al., “Effects of 4- and 6-h Time-Restricted Feeding on Weight and Cardiometabolic Health: A Randomized Controlled Trial in Adults with Obesity,” Cell Metabolism, vol. 32, no. 3, pp. 366-378.e3, Sep. 2020.
doi: 10.1016/j.cmet.2020.06.018

In a randomized controlled trial of obese adults over 8 weeks, 4- and 6-hour time-restricted eating resulted in reductions in body weight and insulin resistance compared to the control group.

Chow et al., “Time-Restricted Eating Effects on Body Composition and Metabolic Measures in Humans who are Overweight: A Feasibility Study,” Obesity, vol. 28, no. 5, pp. 860–869, 2020.
doi: 10.1002/oby.22756

In a randomized controlled trial of 20 adults over 12 weeks, the group with an 8-hour eating window reduced the number of eating occasions, weight, fat mass, lean mass, and visceral fat compared to the control group with unrestricted eating.

Bhutani et al., “Improvements in coronary heart disease risk indicators by alternate-day fasting involve adipose tissue modulations,” Obesity (Silver Spring, Md.), vol. 18, no. 11, pp. 2152–2159, Nov. 2010.
doi: 10.1038/oby.2010.54

Obese subjects were studied over 10 weeks with an alternate-day fasting diet. At the end of the trial, their fat mass decreased, their LDL cholesterol concentration was 25% lower, and their waist circumference was reduced.

Alirezaei et al., “Short-term fasting induces profound neuronal autophagy,” Autophagy, vol. 6, no. 6, pp. 702–710, Aug. 2010.
doi: 10.4161/auto.6.6.12376

Short term fasts (24-48 hours) upregulates autophagy, a mechanism that removes unnecessary or dysfunctional cellular components.

Lamine et al., “Food intake and high density lipoprotein cholesterol levels changes during ramadan fasting in healthy young subjects,” La Tunisie Medicale, vol. 84, no. 10, pp. 647–650, Oct. 2006.
https://pubmed.ncbi.nlm.nih.gov/17193859/

Analyzing young adults who fast during the month of Ramadan (abstaining from food and drink each day from dawn to sunset), blood lipoprotein metabolism improved with an increase of HDL cholesterol. This increase was lost after Ramadan.

Stewart and Fleming, “Features of a successful therapeutic fast of 382 days’ duration,” Postgrad Med J, vol. 49, no. 569, pp. 203–209, Mar. 1973.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495396/

A 27-year-old 456-pound man fasted for 382 days under doctor supervision, losing 276 pounds or 0.72 pounds/day, with no ill effects.

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Erythritol

Storey et al., “Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid,” European Journal of Clinical Nutrition, vol. 61, no. 3, pp. 349–354, Mar. 2007.
doi: 10.1038/sj.ejcn.1602532

Erythritol causes significantly less intestinal distress than xylitol.

Dean et al., “Chronic (1-year) oral toxicity study of erythritol in dogs,” Regulatory toxicology and pharmacology: RTP, vol. 24, no. 2 Pt 2, pp. S254-260, Oct. 1996.
doi: 10.1006/rtph.1996.0106

Erythritol (up to 3.5 g/kg body wt.) is well-tolerated in dogs over a 1 year period. No diarrhea or changes in body weight, plasma electrolyte concentrations, kidneys, organs, or tissues was observed.

Noda et al., “Serum glucose and insulin levels and erythritol balance after oral administration of erythritol in healthy subjects,” European Journal of Clinical Nutrition, vol. 48, no. 4, pp. 286–292, Apr. 1994.
https://pubmed.ncbi.nlm.nih.gov/8039489/

Erythritol does not affect blood levels of glucose or insulin. More than 90% of the ingested erythritol is readily absorbed and excreted in the urine.

Kawanabe et al., “Noncariogenicity of Erythritol as a Substrate,” CRE, vol. 26, no. 5, pp. 358–362, 1992.
doi: 10.1159/000261468

Erythritol is a promising sugar substitute from a dental point of view, as researchers found that it resulted in significantly less dental decay compared to sucrose (table sugar).

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Sucralose

Dalenberg et al., “Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans,” Cell Metabolism, vol. 31, no. 3, pp. 493-502.e7, Mar. 2020.
doi: 10.1016/j.cmet.2020.01.014

Over 10 days, healthy human participants had impaired insulin sensitivity when consuming sucralose with carbohydrates. Insulin sensitivity was not altered by sucralose or carbohydrate consumption alone.

Romo-Romo et al., “Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial,” Am J Clin Nutr, vol. 108, no. 3, pp. 485–491, Sep. 2018.
doi: 10.1093/ajcn/nqy152

In a 2-week randomized control trial of healthy adults, daily sucralose consumption led to a 18% decrease in insulin sensitivity.

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