Continuing Education Activity

Low-carbohydrate (low-carb) diets are a strategy for weight loss. Today, there continues to be an interest in low-carb approaches. While all low-carb approaches reduce the overall intake of carbohydrates, there is no clear consensus on what defines a low-carb diet. Studies have defined low carbohydrate as a percent of daily macronutrient intake or total daily carbohydrate load. This activity reviews the evidence and effectiveness of low-carb approaches in clinical medicine. 

Objectives:

• Identify patients who may benefit from a low-carbohydrate diet based on their health status, goals, and preferences.
• Implement evidence-based guidelines and strategies to prescribe and monitor low-carbohydrate diets for patients effectively.
• Select and recommend appropriate food choices, meal plans, and dietary resources to support patients following a low-carbohydrate diet.
• Collaborate with registered dietitians, nutritionists, and other healthcare professionals to provide comprehensive and coordinated care, ensuring patients receive accurate and consistent guidance.

Introduction

Since 1860, and more recently, in 1972, low carbohydrate (low-carb) diets have been a strategy for weight loss. Today, there continues to be an interest in low-carb approaches. While all low-carbohydrate approaches reduce the overall intake of carbohydrates, no clear consensus on what defines a low-carb diet exists. There are 3 macronutrients—carbohydrates (4 kcal/g), fat (9 kcal/g), and protein (4 kcal/g)—found in food. Therefore, studies have defined low carbohydrate as a percent of daily macronutrient intake or total daily carbohydrate load. This review defines low-carbo diets as follows:

1. Very low-carbohydrate (<10% carbohydrates) or 20 to 50 g/d
2. Low-carbohydrate (<26% carbohydrates) or less than 130 g/d
3. Moderate-carbohydrate (26%-44%)
4. High-carbohydrate (45% or greater)

For reference, the Institute of Medicine proposes Americans obtain 45% to 65% of calories from carbohydrates.[1] This activity reviews the evidence and effectiveness of low-carb approaches in clinical medicine.

Function

Low-carb approaches stem primarily from the hypothesis that lowering insulin, a critical hormone that produces an anabolic, fat-storing state, improves cardiometabolic function, and induces weight loss.[2] This approach has been recently called the carbohydrate-insulin model.[3] Studies have shown low-carb approaches superior to other dietary methods in producing rapid weight loss for the first 6 to 12 months.[4][5][6] 

While diets inducing weight loss produce a caloric deficit, the mechanism of low-carb diets remains debated. When reducing carbohydrates from the diet, the macronutrient intake of fat and protein generally increases to compensate for the reduction of carbohydrates.

One hypothesis supporting why low-carb approaches produce rapid weight loss compared to other diets is that fats and protein increase satiety and produce less concomitant hypoglycemia. This increase in satiety and less rebound hypoglycemia reduces hunger and overall food intake and produces a caloric deficit. Another hypothesis contends that low-carb diets can produce a higher metabolic burn than high-carb diets. Recent studies show a metabolic advantage of approximately 200 to 300 more calories burned compared to an isocaloric high-carb diet.[2][7] However, these theories remain controversial.[8]

The ketogenic (keto) diet, a specific low-carb version, deserves mention. Keto diets restrict carbohydrates to induce nutritional ketosis and typically limit carbs to 20 to 50 grams daily. Restricting carbs to under 50 grams induces glycogen depletion and ketone production by mobilizing fat stored in adipose tissue. Nutritional ketosis produces ketone bodies (acetoacetate, acetone, and beta-hydroxybutyrate) and is measurable as serum or urinary ketones. Nutritional ketosis generally increases serum ketones from 1 mmol/L to 7 mmol/L but does not produce metabolic acidosis. Diabetic ketoacidosis, by definition, includes metabolic acidosis, hyperglycemia, and serum ketones (generally over 20 mmol/L).[9]

The term net carbs refers to the total amount of fully digestible carbohydrates contained in a meal. Net carbs are calculated by subtracting the whole amount of fiber and half the amount of sugar alcohols from the amount of total carbs. The nutritional impact of using net carbs is to help the patient choose foods that are higher in fiber.

Despite the debate, numerous systematic reviews demonstrate that low-carb diets are as effective, if not more effective, for weight loss compared to other diets. The evidence for benefits and concerns for low-carb will be further delineated below.

Issues of Concern

Several theoretical concerns about the long-term safety of low-carb diets deserve mention. Low-carb diet safety concerns relate to ketosis, long-term cardiovascular safety, lipid levels, and renal effects.

Ketosis

Nutritional ketosis can be induced in the keto diet, the induction phase, and when carb load is limited to less than 10% of macronutrient intake or 20 to 50 g/d of carbohydrates. However, there is no evidence that very low-carb intake produces metabolic ketoacidosis and remains safe in patients, even those with type 2 diabetes.[9][10] 

While there have been cases of diabetic ketoacidosis (DKA) with concomitant SGLT2 inhibitors in patients with type 2 diabetes, it is unclear if the very low-carb approach increases the risk of DKA with SGLT2 use. The recommendation is to use caution with using ketogenic diets with the concomitant use of SGLT-2 inhibitors.[11]

Mortality and Cardiovascular Safety

Several studies link low-carb diets to increased mortality. Epidemiological studies and meta-analyses have shown an increased mortality risk with a carbohydrate intake of less than 40%.[12][13] However, the recent Prospective Urban Rural Epidemiology (PURE) study, a large prospective nutrition study involving over 135,000 participants across the globe, found a relationship between increased mortality and higher carbohydrate intake and lower mortality associated with higher fat intake.[14] 

Another prospective cohort study found that healthy low-carb and low-fat diets were associated with lower mortality, and unhealthy low-carb and low-fat diets were associated with higher mortality.[15] This suggests that the quality of the food matters, not just the level of macronutrient intake. The ongoing effect is unclear; more long-term, randomized studies are prudent.

Lipid Response

Incorporating more fat and protein in response to reducing dietary carbs has led to concerns about the effect of low-carb dieting on lipids, specifically LDL cholesterol. Recent systematic reviews of low-carb diets on lipids demonstrate a neutral-to-small increase in LDL, a favorable triglycerides reduction, and an increase in HDL cholesterol, particularly in those assigned to the very–low-carb intervention.[16][17] 

Research recently indicated that a subset of lean individuals, called lean mass hyper-responders, might have a hyper LDL response with ketogenic diets.[18] Due to the varied and individualized response, recommendations are for baseline fasting lipid profile, periodic testing, and shared decision-making.

Renal Function

With a potentially higher protein intake on low-carb diets, some have expressed concerns about renal function. However, depending on specific goals, athletes should ingest protein loads to optimize muscle protein synthesis (1.6 g/kg) or endurance sports (0.8 g/kg).[19][20] 

Encouraging higher protein loads to support physical activity can also help improve body composition and metabolic adaptations. No data generally associates high-protein load with worsening kidney function in those with normal kidney function.[21] To prevent further renal deterioration, a low-protein or very–low-protein diet (0.2-0.8 g/kg/d) may be recommended for those with chronic kidney disease.[22]

Clinical Significance

The study of low-carb diets has centered on weight loss in obese and overweight people and patients with or at risk for cardiometabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Ketogenic diets have also been used for seizure disorders and, more recently, have found use in the athletic population as an alternative fuel for performance and health.

Weight Loss

Most research on low-carb approaches has shown that a low-carb diet, specifically a ketogenic diet, induces rapid weight loss induction. Initial weight loss is due partly to water loss, but fat loss occurs with adherence to the low-carb approach. With all dietary interventions, as adherence to the diet wanes, the weight loss effect becomes similar to other nutritional approaches after one year.[23] 

Notably, most low-carb diet studies generally use an ad-libitum approach to caloric intake (limiting carbs instead), while most comparison diets are calorie-restricted. In general, shared decision-making is a valid and person-centered approach to determining nutritional strategies for weight loss.

Type 2 Diabetes

Before medications, carbohydrate control has been the cornerstone of glycemic control in type 1 and type 2 diabetes. Dietary carbohydrates increase insulin needs, and reduction of carbohydrate intake can improve glycemic control.[24] A recent study demonstrated a significant reduction of insulin and oral medications and hemoglobin A1c reduction with ketogenic approaches while demonstrating a high adherence to the intervention at 12 months.[25][26] Also, markers of cardiometabolic risk factors improved.[27] A systematic review and meta-analysis found low-quality evidence that low-carb approaches increase type 2 diabetes remission and are generally safe.[28]  

Approaches to nutritional lifestyle and approaches to diabetes medical nutrition therapy have included a low-carb approach as an option in recent guidelines.[29][30][31] Recent prospective and randomized controlled trials have consistently benefited glycemic control, weight loss, and sustained medication reduction using a very low-carb approach, less than 14% of energy from carbohydrates.[32][33][34]

As patients with type 2 diabetes improve glycemic control, lower weight, and reduce medication use, hemoglobin A1c may fall below the threshold for diagnosis. Recent data demonstrate that remission from type 2 diabetes may be possible.[35] A consensus statement from the American Diabetic Association, the Endocrine Society, the European Association for the Study of Diabetes, Diabetes UK, and the Diabetes Surgery Summit defines remission as a hemoglobin A1c of less than 6.5% for at least 3 months without using glycemic lowering medications.[36]

Cardiovascular Risk Factors

As mentioned above, the effect of low-carb diets on cardiovascular risk factors continues to be controversial. While a few studies have demonstrated an increase in LDL cholesterol with low-carb diets, others showed negligible changes. However, other metabolic markers, such as lowering triglycerides and increases in HDL, have been demonstrated with low-carb diets.[4][27][17]

Initiation of a Low-Carb Lifestyle

After a shared decision-making process with the patient, there are numerous ways to start a patient on a low-carb diet. Low-carb nutrition may be advisable for those who desire healthy or athletic performance, weight loss, improvement of glycemic control for type 1 or 2 diabetes, or a seizure disorder.

• First, understanding macronutrients and their relation to food is critical to patient counseling.
• Secondly, determine the patient's desire for either small steps or a rapid induction phase through motivational interviewing and S.M.A.R.T (specific, measurable, attainable, realistic, and time-bound) goal setting.
• Limiting added sugar (sucrose) and refined carbohydrates is critical in improving food quality and will generally reach a moderate carbohydrate (<45% carbohydrates) level.
• One method to initiate low-carb is through a rapid induction phase of 2 to 4 weeks, with 20 to 50 grams of carbohydrates to induce nutritional ketosis. Ad libitum vegetables that grow above the ground and are lower in carbohydrate content are encouraged. Additionally, carbs should be limited to those found in whole, unprocessed food.
• Finally, after the induction phase, depending on goals, patients can remain in the keto phase or slowly add healthy carbohydrates from whole, unprocessed vegetables and low-glycemic, high-fiber fruit (eg, berries).

Maintenance of a Low-Carb Lifestyle

If limited initially or during the induction phase, full-fat dairy, legumes, and whole grains can also be added during this maintenance phase as long as goals are maintained and tolerated without any hypersensitivity or an adverse response. The lifelong maintenance phase can then continue per patient preference. Periodic monitoring of cardiovascular risk markers and control of cardiometabolic disease should also be a priority. Those with type 2 diabetes require close monitoring for hypoglycemia, and reducing insulin or hypoglycemic medications is prudent with rapid reductions in fasting glucose.[37] 

Other Issues

Ketogenic diets have been used successfully since 1920, before the existence of medications for epilepsy.[9][38] Recent studies have shown that acne, cancer, nonalcoholic fatty liver disease, polycystic ovary syndrome, and Alzheimer disease may improve with ketogenic diets.[9][39] 

The use of keto diets to provide sustained and steady fuel for endurance sports in athletic individuals and the optimization of body composition in high-intensity training for the recreational population have also undergone testing.[40][41]

Enhancing Healthcare Team Outcomes

Interprofessional care coordination involving clinicians, pharmacists, dieticians, and nutritionists working collaboratively, providing patient education, and monitoring patient progress and health status is the optimal approach to implementing a low-carb diet to achieve health goals.

Nursing, Allied Health, and Interprofessional Team Interventions

Clinical Pharmacist

Patients on chronic medications may require rapid medication adjustments while on a low-carbohydrate diet. Recently a small randomized controlled study demonstrated improved glycemic control and reduction of medication use led by a community-based clinical pharmacist.[42] 

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Trumbo P, Schlicker S, Yates AA, Poos M., Food and Nutrition Board of the Institute of Medicine, The National Academies. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc. 2002 Nov;102(11):1621-30. [PubMed: 12449285]

2.

Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, Wong WW, Ludwig DS. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018 Nov 14;363:k4583. [PMC free article: PMC6233655] [PubMed: 30429127]

3.

Ludwig DS, Ebbeling CB. The Carbohydrate-Insulin Model of Obesity: Beyond "Calories In, Calories Out". JAMA Intern Med. 2018 Aug 01;178(8):1098-1103. [PMC free article: PMC6082688] [PubMed: 29971406]

4.

Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS, Brehm BJ, Bucher HC. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Feb 13;166(3):285-93. [PubMed: 16476868]

5.

Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013 Oct;110(7):1178-87. [PubMed: 23651522]

6.

Tobias DK, Chen M, Manson JE, Ludwig DS, Willett W, Hu FB. Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2015 Dec;3(12):968-79. [PMC free article: PMC4667723] [PubMed: 26527511]

7.

Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS. Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA. 2012 Jun 27;307(24):2627-34. [PMC free article: PMC3564212] [PubMed: 22735432]

8.

Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, Yannai L. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab. 2015 Sep 01;22(3):427-36. [PMC free article: PMC4603544] [PubMed: 26278052]

9.

Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013 Aug;67(8):789-96. [PMC free article: PMC3826507] [PubMed: 23801097]

10.

Noakes TD, Windt J. Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review. Br J Sports Med. 2017 Jan;51(2):133-139. [PubMed: 28053201]

11.

Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care. 2015 Sep;38(9):1638-42. [PubMed: 26294774]

12.

Noto H, Goto A, Tsujimoto T, Noda M. Low-carbohydrate diets and all-cause mortality: a systematic review and meta-analysis of observational studies. PLoS One. 2013;8(1):e55030. [PMC free article: PMC3555979] [PubMed: 23372809]

13.

Seidelmann SB, Claggett B, Cheng S, Henglin M, Shah A, Steffen LM, Folsom AR, Rimm EB, Willett WC, Solomon SD. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health. 2018 Sep;3(9):e419-e428. [PMC free article: PMC6339822] [PubMed: 30122560]

14.

Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V, Iqbal R, Kumar R, Wentzel-Viljoen E, Rosengren A, Amma LI, Avezum A, Chifamba J, Diaz R, Khatib R, Lear S, Lopez-Jaramillo P, Liu X, Gupta R, Mohammadifard N, Gao N, Oguz A, Ramli AS, Seron P, Sun Y, Szuba A, Tsolekile L, Wielgosz A, Yusuf R, Hussein Yusufali A, Teo KK, Rangarajan S, Dagenais G, Bangdiwala SI, Islam S, Anand SS, Yusuf S., Prospective Urban Rural Epidemiology (PURE) study investigators. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet. 2017 Nov 04;390(10107):2050-2062. [PubMed: 28864332]

15.

Shan Z, Guo Y, Hu FB, Liu L, Qi Q. Association of Low-Carbohydrate and Low-Fat Diets With Mortality Among US Adults. JAMA Intern Med. 2020 Apr 01;180(4):513-523. [PMC free article: PMC6990856] [PubMed: 31961383]

16.

Gjuladin-Hellon T, Davies IG, Penson P, Amiri Baghbadorani R. Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. Nutr Rev. 2019 Mar 01;77(3):161-180. [PubMed: 30544168]

17.

Lu M, Wan Y, Yang B, Huggins CE, Li D. Effects of low-fat compared with high-fat diet on cardiometabolic indicators in people with overweight and obesity without overt metabolic disturbance: a systematic review and meta-analysis of randomised controlled trials. Br J Nutr. 2018 Jan;119(1):96-108. [PubMed: 29212558]

18.

Norwitz NG, Feldman D, Soto-Mota A, Kalayjian T, Ludwig DS. Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a "Lean Mass Hyper-Responder" Phenotype. Curr Dev Nutr. 2022 Jan;6(1):nzab144. [PMC free article: PMC8796252] [PubMed: 35106434]

19.

Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018 Mar;52(6):376-384. [PMC free article: PMC5867436] [PubMed: 28698222]

20.

Thomas DT, Erdman KA, Burke LM. American College of Sports Medicine Joint Position Statement. Nutrition and Athletic Performance. Med Sci Sports Exerc. 2016 Mar;48(3):543-68. [PubMed: 26891166]

21.

Martin WF, Armstrong LE, Rodriguez NR. Dietary protein intake and renal function. Nutr Metab (Lond). 2005 Sep 20;2:25. [PMC free article: PMC1262767] [PubMed: 16174292]

22.

Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev. 2018 Oct 04;10(10):CD001892. [PMC free article: PMC6517211] [PubMed: 30284724]

23.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 07;297(9):969-77. [PubMed: 17341711]

24.

Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI, Nielsen JV, Krarup T, Saslow L, Roth KS, Vernon MC, Volek JS, Wilshire GB, Dahlqvist A, Sundberg R, Childers A, Morrison K, Manninen AH, Dashti HM, Wood RJ, Wortman J, Worm N. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015 Jan;31(1):1-13. [PubMed: 25287761]

25.

McKenzie AL, Hallberg SJ, Creighton BC, Volk BM, Link TM, Abner MK, Glon RM, McCarter JP, Volek JS, Phinney SD. A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes. JMIR Diabetes. 2017 Mar 07;2(1):e5. [PMC free article: PMC6238887] [PubMed: 30291062]

26.

Hallberg SJ, McKenzie AL, Williams PT, Bhanpuri NH, Peters AL, Campbell WW, Hazbun TL, Volk BM, McCarter JP, Phinney SD, Volek JS. 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. Diabetes Ther. 2018 Apr;9(2):583-612. [PMC free article: PMC6104276] [PubMed: 29417495]

27.

Bhanpuri NH, Hallberg SJ, Williams PT, McKenzie AL, Ballard KD, Campbell WW, McCarter JP, Phinney SD, Volek JS. 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. 2018 May 01;17(1):56. [PMC free article: PMC5928595] [PubMed: 29712560]

28.

Goldenberg JZ, Day A, Brinkworth GD, Sato J, Yamada S, Jönsson T, Beardsley J, Johnson JA, Thabane L, Johnston BC. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. 2021 Jan 13;372:m4743. [PMC free article: PMC7804828] [PubMed: 33441384]

29.

Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. 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). Diabetes Care. 2018 Dec;41(12):2669-2701. [PMC free article: PMC6245208] [PubMed: 30291106]

30.

Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, Mitri J, Pereira RF, Rawlings K, Robinson S, Saslow L, Uelmen S, Urbanski PB, Yancy WS. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report. Diabetes Care. 2019 May;42(5):731-754. [PMC free article: PMC7011201] [PubMed: 31000505]

31.

ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Young-Hyman D, Gabbay RA, on behalf of the American Diabetes Association 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 01;46(Supple 1):S68-S96. [PMC free article: PMC9810478] [PubMed: 36507648]

32.

Tay J, Thompson CH, Luscombe-Marsh ND, Wycherley TP, Noakes M, Buckley JD, Wittert GA, Yancy WS, Brinkworth GD. Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes Obes Metab. 2018 Apr;20(4):858-871. [PubMed: 29178536]

33.

Tay J, Luscombe-Marsh ND, Thompson CH, Noakes M, Buckley JD, Wittert GA, Yancy WS, Brinkworth GD. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. Am J Clin Nutr. 2015 Oct;102(4):780-90. [PubMed: 26224300]

34.

Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr. 2013 Mar;97(3):505-16. [PubMed: 23364002]

35.

Zhang Y, Yang Y, Huang Q, Zhang Q, Li M, Wu Y. The effectiveness of lifestyle interventions for diabetes remission on patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Worldviews Evid Based Nurs. 2023 Feb;20(1):64-78. [PubMed: 36480153]

36.

Riddle MC, Cefalu WT, Evans PH, Gerstein HC, Nauck MA, Oh WK, Rothberg AE, le Roux CW, Rubino F, Schauer P, Taylor R, Twenefour D. Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. Diabetes Care. 2021 Aug 30;44(10):2438-44. [PMC free article: PMC8929179] [PubMed: 34462270]

37.

Cucuzzella M, Riley K, Isaacs D. Adapting Medication for Type 2 Diabetes to a Low Carbohydrate Diet. Front Nutr. 2021;8:688540. [PMC free article: PMC8380766] [PubMed: 34434951]

38.

Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2018 Nov 07;11(11):CD001903. [PMC free article: PMC6517043] [PubMed: 30403286]

39.

Broom GM, Shaw IC, Rucklidge JJ. The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease. Nutrition. 2019 Apr;60:118-121. [PubMed: 30554068]

40.

Volek JS, Freidenreich DJ, Saenz C, Kunces LJ, Creighton BC, Bartley JM, Davitt PM, Munoz CX, Anderson JM, Maresh CM, Lee EC, Schuenke MD, Aerni G, Kraemer WJ, Phinney SD. Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism. 2016 Mar;65(3):100-10. [PubMed: 26892521]

41.

Kephart WC, Pledge CD, Roberson PA, Mumford PW, Romero MA, Mobley CB, Martin JS, Young KC, Lowery RP, Wilson JM, Huggins KW, Roberts MD. The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study. Sports (Basel). 2018 Jan 09;6(1) [PMC free article: PMC5969192] [PubMed: 29910305]

42.

Durrer C, McKelvey S, Singer J, Batterham AM, Johnson JD, Gudmundson K, Wortman J, Little JP. A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes. Nat Commun. 2021 Sep 10;12(1):5367. [PMC free article: PMC8433183] [PubMed: 34508090]

Disclosure: Robert Oh declares no relevant financial relationships with ineligible companies.

Disclosure: Brian Gilani declares no relevant financial relationships with ineligible companies.

Disclosure: Kalyan Uppaluri declares no relevant financial relationships with ineligible companies.