The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

Shivam Joshi; Robert J. Ostfeld; Michelle McMacken

doi:10.1001/jamainternmed.2019.2633

Viewpoint

July 15, 2019

The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

Shivam Joshi, MD^1,2; Robert J. Ostfeld, MD, MSc³; Michelle McMacken, MD^1,2

Author Affiliations Article Information

¹Division of General Internal Medicine, Department of Medicine, New York University School of Medicine, New York
²Department of Medicine, NYC Health + Hospitals/Bellevue, New York
³Division of Cardiology, Montefiore Health System, Bronx, New York

JAMA Intern Med. 2019;179(9):1163-1164. doi:10.1001/jamainternmed.2019.2633

The ketogenic diet has recently received much attention for its promise of treating obesity and type 2 diabetes. However, the enthusiasm for its potential benefits exceeds the current evidence supporting its use for these conditions. Although the temptation is great to recommend a potentially novel approach for otherwise difficult-to-treat diseases, it is important to remain grounded in our appraisal of the risks, benefits, and applicability of the diet to avoid unnecessary harm and costs to patients.

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12 Comments for this article

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July 16, 2019

Diabetes and Metabolic Syndrome can be reversed on Keto

Stephen Riggs, MD | MercyOne Waterloo, IA

I have been in the practice of internal medicine for over 30 years. In all that time I never took anyone off their insulin or rarely reduced their medications unless they had gastric bypass surgery or something as drastic. After implementing the ketogenic diet for the past year I daily am seeing patients come off insulin and reverse their diabetes, correct their hypertension, feel great, reduce inflammation and chronic pain, improve cognitive scores, correct their dyslipidemia, and improve athletic performance. As with most other physicians my nutritional education was poor and I considered it irrelevant. Today, the low carb approach is by far the biggest tool in my toolbox. So I read with disappointment the Viewpoint by Joshi et.al., replaying the old yarn about the "dangers" of the ketogenic diet and lack of evidence. Actually, though not yet mainstream the ketogenic diet has been extensively studied since its development at Mayo in 1921. Over 30 head to head trials confirm that keto is the king of weight loss diets and that nutritional ketosis (not to be confused with DKA) is a natural physiological condition that not only helps fuel the brain, heart, muscle and gut but current research is exploding with evidence that ketones are also signaling molecules that turn on many biologically beneficial pathways that reduce inflammation, lower seizure activity, promote glycogen sparing, increase athletic performance and especially lower insulin resistance and can even reduce or eliminate the need for diabetes medications. There are currently over 30 clinical trials ongoing looking at the ketogenic diet and cancer therapy for its profound metabolic effects. There have been far more studies on the ketogenic diet than either vegetarian, DASH, or the Mediterranean diet. In the words of Duke University researcher Eric Westman "If Keto were a drug it would already have FDA approval."There is no drug that can do what the low carb diet can. There are many medical interventions that we clinicians in the trenches do based solely on what we are told in the literature based on p-values and confidence intervals based on massive population studies; we take it on faith and clinical practice guidelines. Not so with keto. The evidence is so remarkable and patients get better literally right before our eyes. I have had patients that I diagnosed with diabetes over 15 years ago and gradually ramped up their medications including > 100 units of insulin and within 2-3 months most are off insulin and their other meds as well. What drug can do that? In the words of Elliot Joslin (founder of Harvard's Joslin Diabetes Center) before the advent of insulin, the evidence for the low carbohydrate treatment of diabetes is so obvious that "no clinical trials are needed." My experience with hundreds of real patients – patients I have diagnosed and treated for 15, 20 or even 30 years just watching them get sicker and fatter and within months seeing their health rebound and diabetes resolve is hard to ignore. I only hope the medical establishment will catch up to what is being rapidly discovered here "in the trenches." But don't take my word for it. For those interested in the massive amount of evidence for the ketogenic diet I would encourage the Ketogenic Nutrition Course by the ANA (American Nutrition Association) for starters. My own conclusion after doing a deep dive on this over the past year is that this will be standard of care in 10 years. In 30 years, we will look back on the decision to take fat out of our diet as the biggest public health mistake we ever made.

CONFLICT OF INTEREST: None Reported

July 17, 2019

Ketogenic Diet for Obesity and Diabetes

David Martin, MD, FACG | Pinehurst Medical Clinic

Obviously the authors of this paper have not recommended a very low carbohydrate diet (ketogenic diet) to their patients. If they had they would be amazed at how well people do. Patients lose weight, diabetes comes under better control and often they can get off meds. One of my GI techs has lost 90 pounds and no longer meets criteria for polycystic ovary syndrome. In addition to weight loss and improvement in diabetes, reflux symptoms often go away and patients are able to get off PPI's. Fatty liver improves with normalization of transaminases. Joint pains go away. I have a 32 year old male with type 2 diabetes and ulcerative colitis. His ulcerative colitis is well controlled with a biologic, but was having severe joint pain. Wasn't sure whether the biologic was the cause of the joint pain, so switched from Remicade to Humira. Two months later recurrence of joint pain. Switched to Xeljanz. Two weeks later the joint pains much worse. Rheumatology had nothing to offer (NSAIDs would make the colitis worse and steroids would make the diabetes worse. Could potentially try Stelara, but hate to burn through all our biologic options.) With the severe joint pains, finally able to convince him to do the ketogenic diet. Within 3 days he had significantly less joint pain. People also get relief of headaches. IBS-D comes under control. If patients stick with it long enough IBS-C comes under control. I've been using low carb diets, beginning with the specific carbohydrate diet, since 2010. Main difference in SCD and ketogenic diet is emphasis on getting more fat in the diet, which makes it more sustainable-not hungry.

CONFLICT OF INTEREST: None Reported

July 18, 2019

Agree with the authors and not with the comments given

Karen Freijer, PhD | Nutrition and Nutrition Economics

So great that this paper has been published!
One should be very careful when adapting a food pattern on one's own-especially when it concerns patients! Nutrition is a real profession for which one has to study at least for 4 years!!! It is not something one can learn overnight or by reading a chapter in a book! And nutrition is the basis of our existence and health. It can be very dangerous to just adapt your diet without really knowing what to take into account. Undernutrition in the longer term with all the complications can be the result of using a diet without knowing what to take into account. Physicians are the specialists in the field of medicine, but only dietitians/nutritionists are the specialists in the field of nutrition. A physician is also not giving physiotherapy exercises to their patients! So don’t do this for nutrition! You can really harm your patient in the longer term and then it is very hard to reverse the problems that have arisen! Please consult a nutritionist/dietitian when you want to give your patients advice on nutrition!!!

CONFLICT OF INTEREST: None Reported

July 19, 2019

Authors are misguided

Jay Wortman, BSc MD CCFP | University of British Columbia

I personally reversed my T2DM and Mets over 16 yrs ago by adopting a keto diet. I have maintained a 35 lb wt loss and normal HbA1c, lipid profile and blood pressure over that period. I recently had a CAC scan and my score was zero. All this with zero medication. I currently use a keto diet with patients who have any manifestation of insulin resistance plus any who have an inflammatory or CNS condition. I have many success stories. The idea that physicians are not able to safely implement diet change is nonsense. It is important for physicians to understand the specific needs of patients who start a keto diet and to be proactive in managing the inevitable reduction in medications but otherwise it is not rocket science to reduce carbs and encourage a whole food low carb diet.

CONFLICT OF INTEREST: Member of Scientific Advisory Board, Atkins Nutritionals Inc

July 19, 2019

Please Represent the Full Picture of the Research

Kelly Sylvester, PhD | University

There are plenty of studies (many RCTs) available showing the benefits of a low-carbohydrate diet on disease risk. And they are not difficult to locate. To make claims, please represent the full body of evidence, not just one side.

CONFLICT OF INTEREST: None Reported

July 19, 2019

The Ketogenic Diet for Obesity and Diabetes—Evidence Outpaces Enthusiasm

Angela Stanton, PhD | self employed

The authors of this paper(1) have ignored critical research that specifically show that neither calorie restriction nor weight loss is the key working force behind the success of the ketogenic diet. A recent article specifically targeted this problem, presented this frequently voiced assumption and proved it incorrect(2).

In addition, the ketogenic diet leads to the ketogenic metabolic process (ketosis), which is not a fad. People were in ketosis as fetuses(3) in their mother’s womb(4,5), were born in ketosis(6), remained in ketosis through most of nursing, and also all through their childhood nights while sleeping(7).

The fetus in the womb if hardly on a calorie-restricted diet. It is using ketones to build vital organs--such as the brain--made primarily of lipids.

The ketogenic diet is the best way by which ketosis is achieved and ketosis is clearly a natural human metabolic process that is advantageous for healthy development of an infant and beneficial for healthy body recovery and maintenance for adults.

1 Joshi, S., Ostfeld, R. J. & McMacken, M. The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces EvidenceThe Ketogenic Diet for Obesity and DiabetesThe Ketogenic Diet for Obesity and Diabetes. JAMA Internal Medicine, doi:10.1001/jamainternmed.2019.2633 (2019).
2 Hyde, P. N. et al. Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight 4, doi:10.1172/jci.insight.128308 (2019).
3 Herrera, E. & Amusquivar, E. Lipid metabolism in the fetus and the newborn. Diabetes/Metabolism Research and Reviews 16, 202-210, doi:doi:10.1002/1520-7560(200005/06)16:3<202::AID-DMRR116>3.0.CO;2-# (2000).
4 Paterson, P., Sheath, J., Taft, P. & Wood, C. MATERNAL AND FOETAL KETONE CONCENTRATIONS IN PLASMA AND URINE. The Lancet 289, 862-865, doi:10.1016/S0140-6736(67)91426-2 (1967).
5 Orczyk-Pawilowicz, M. et al. Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy. PloS one 11, e0152740-e0152740, doi:10.1371/journal.pone.0152740 (2016).
6 Kimura, R. E. & Warshaw, J. B. Metabolic Adaptations of the Fetus and Newborn. Journal of Pediatric Gastroenterology and Nutrition 2, 12-15 (1983).
7 Cahill, G. F. Starvation in man. N Engl J Med 282, doi:10.1056/nejm197003052821026 (1970).

CONFLICT OF INTEREST: None Reported

July 21, 2019

It's all about the context, and the alternatives

Omer Berner | Ben Gurion University

There's a significant difference between reviewing this diet as a lifestyle modification for the healthy population or for the diabetic population. Major concerns have been raised about the outcomes of a keto diet, including worsening glucose intolerance (https://www.ncbi.nlm.nih.gov/pubmed/31067015)
.
However, in the clinic, one has to think about the pros, cons and alternatives for his specific diabetic patient. In a patient with poor lifestyle and glycemic control, on a lot of medications, proposing a keto diet, despite it's possible negative effects in some aspects, might do more good then bad if indeed the diet enables this specific patient to get off his medications and lowering his HbA1C dramatically.

CONFLICT OF INTEREST: None Reported

July 28, 2019

I too disagree.

Adeline Louie, MD | retired

I too disagree with the authors’ assertions. I myself had astronomical lipid values and did not want to be snowed with statins or fibrates. So I undertook a short experiment on myself. I went on a low carb high animal fat diet for 5 weeks. I had no restrictions on calories, and probably took in more calories than normal, as I ate lots of fatty meat. The result: I dropped all my lipid values, especially my triglycerides which decreased close to a 1000 points. And HDL increased. I also sustained a several pound weight loss. All this on no lipid drugs. My A1C and fasting glucose dropped into the normal range too. I will note that I am not obese, and have only a borderline A1C. I have no doubt that diet can reverse what is a modern dietary disease, that of obesity and diabetes Type II.

CONFLICT OF INTEREST: None Reported

July 29, 2019

Toxicity of Lipophilic Chemicals

Harold Zeliger, Ph.D. | Zeliger Research & Consulting

The Keto diet ignores the proven fact that the high fat ingested results in the adsorption of greatly increased quantities of highly toxic lipophiles such as TCDD, PCBs and chlorinated pesticides. These are stored in adipose tissue for decades and slowly, but continually partition into blood and are carried throughout the body.

CONFLICT OF INTEREST: None Reported

August 3, 2019

Still Controversial...after all these years.

Alexander Anderson, Various | M.D. AndTrade Ltd.

Not having ever worked in academia, basic research or under large corporate governance but, along with some of the other authors of comments here, in those ubiquitous "trenches", acknowledgement that after more than 7 decades of data and research in this area, that questions still remain as to the basic validity and efficacy of "KETO" is, to put it mildly, rather astonishing. "Meta-analysis of 13 studies lasting longer than a year" along with "a meta-analysis of 32 controlled feeding studies" notwithstanding.

Some of what this continuing controversy clearly suggests is the following:

1) What conclusions are drawn depends on the information that is arbitrarily select to evaluate;

2) The size of the frame of effect, conditions and outcomes selected to evaluate in the analysis;

3) Selection factors that invariably will influence the outcomes of your test subjects and rarely consider genetic influences.

4) That, like political prejudices, it is unlikely only facts and objective physical realities will influence and inform "objective and scientific" judgments.

CONFLICT OF INTEREST: None Reported

August 3, 2019

Refreshing Commentary

John Kaplan, MD | Dr. John's Nutrition Health

Thank you for listing the various potential side effects of the ketogenic diet. A majority of those attempting the ketogenic diet do not achieve actual or sustained ketosis. For most, the diet is practiced as another rendition of the low carb diets that have periodically found temporary popularity in the past- Atkins, Paleo, Zone, Southbeach, etc. Thy are all high meat/fat diets. As the article notes, all cause mortality is higher in this group than on a plant- based low fat nutritional plan.
The epidemic of diabetes is not addressed by the ketogenic diet. Diabetes is not caused by carbohydrates. A high animal fat standard American diet diet causes massive amount of intramyocellular lipid concentration primarily in muscle, liver, and pancreatic cells. The fat is stored in places not designed for this heavy lipid load respond by becoming Insulin resistant. Insulin resistance raises intravascular glucose. Hyperglycemia is a symptom of diabetes, not the cause!
When we calorie restrict patients they lose weight. This is also true for the ketogenic plan. Calorie restriction which also restricts carbohydrates lowers hyperglycemia. The doctor and patient are falsely encouraged by a temporary lowering of blood glucose and HA1C levels. This is at the expense of a health engendering supply of the body's primary energy source from dietary carbohydrate. Insulin resistance on a ketogenic diet proceeds and intensifies on this high animal fat diet. Intensification of risks for cardiovascular disease ( heart disease and stroke), erectile dysfunction, and even dementia also increase on this high meat/fat diet as well.
Only low fat plant- based diets have demonstrated the ability to reverse cardiovascular disease and diabetes (see studies by Caldwell Essylsten, Dean Ornish, and Neil Barnard)
The medical profession would greatly benefit by adding nutrition training as a core educational priority in medical schools.

CONFLICT OF INTEREST: None Reported

September 9, 2019

Benefits of true ketogenic diets versus purported ketogenic diets

Irving Cohen, MD, MPH | Foundation for Prevention

It is easy to set up a straw man to tear apart. The authors use the singular term "the ketogenic diet" and rely on meta-analysis of various ketogenic diets. Is this paper addressing therapeutic diets, weight loss diets, diabetes recovery diets or simply anything called ketogenic? Modern understanding of the clinical value of ketogenic diet extends a century (1), and earlier ketogenic diets (2,3) date to antiquity. Woodyatt (4) in 1921 created a formula for calculating the ketogenic ratio (KR) predicting the dietary mixture to maintain ketosis in a therapeutic diet. Metcalf and Moriarty (5) provided a simpler but less accurate formula, KR=f/(p+C). That simple method remains in use, although the more accurate formula can be easily used with a computer. Both were intended only for a therapeutic diet not producing weight loss. Mistaken use for weight-loss diets produces misleading results. A decade ago, I introduced the term Total Ketogenic Ratio (TKR) to include energy from liberated lipid when a diet was hypocaloric (6). Modifying Woodyatt's formula, it provides a tool to predict a diet's ability to cause ketosis.
Benefits differ for therapeutic diets, weight loss diets, diabetes control diets or a mixture. In therapeutic ketogenic diets (7) used for seizure control that benefit is believed to be the result of increased gamma amino butyric acid (GABA) (8).
When a hypocaloric ketogenic diet is used in weight reduction, the increase in GABA is the likely cause of the reported anxiolytic effect. This contrasts to the anxiogenic effect of a falling glucose level, which triggers cravings in other weight loss dieting. This difference in food cravings obvious to dieters but missed in controlled feeding studies the authors mention.
In type II diabetics and prediabetics the reduced need for insulin leads to reduced insulin resistance and allows a return to normal glucose values while weaning off medication. Weaning from medication allows targeting normal glucose levels without risking hypoglycemia, which cannot be said when treated pharmacologically.
Other clinical situations where a therapeutic ketogenic diet may be useful can be found in Paoli's review (9).

1 Wilder RM: The effects of ketonemia on the course of epilepsy. Clinical Bulletin 1921, 2:307.
2 Ebstein W: Corpulence and its treatment on physiological principles, New edn. London: H. Grevel & Co.; 1890.
3 Littré MPÉ: Du rêgìme â suîvre pour pedre ou gagner de l'embonpoînt. In: Oeuvres Complètes D'Hippocrate, traduction nouvelle avec le texte Greg. vol. 6. Paris: Chez J.B. Baillière; 1849: 76-79.
4 Woodyatt RT: Objects and method of diet adjustment in diabetes. Archives of Internal Medicine 1921, 28(2):125-141.
5 Metcalf KM, Moriarty ME: A clinical study of epileptic children treated by ketogenic diet. Boston Medical & Surgical Journal 1927, 196(3):89-96.
6 Cohen IA: A model for determining Total Ketogenic Ratio (TKR) for evaluating the ketogenic property of a weight-reduction diet. Medical Hypotheses 73 (2009) 377-381.
7 Freeman JM, Vining EPG, Casey JC, McGrogan JR: The ketogenic diet revisited. In: Epilepsy Problem Solving in Clinical Practice. Edited by Schmidt D, Schacter SC. London: Martin Dunitz; 2000: 315-324.
8 Zhang Y, Xu J, Zhang K, Yang W, Li B: The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms. Curr Neuropharmacol. 2018;16(1):66-70.
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.

CONFLICT OF INTEREST: I am the author of several books and an e-learning course for patients on the use of diet for diabetes recovery ans weight-loss.

The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

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