The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

Joshi, Shivam; Ostfeld, Robert J.; McMacken, Michelle

doi:10.1001/jamainternmed.2019.2633

Cited by 100 publications

(76 citation statements)

References 10 publications

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“…Keto-diets, which are also high in protein and animal fats, are gaining popularity across different healthcare systems throughout the world as a recommended dietary intervention for adults with diabetes [20]. Despite its immediate appeal for the use of type 2 diabetes, the ketogenic diet has not been as effective for glycemic control or weight loss in randomized, controlled trials as often touted and may carry additional risks to long-term health [21]. Furthermore, previous and emerging data (Table 1) suggest that high DPI in these diets, by way of causing increased intra-glomerular pressure with resultant glomerular hyperfiltration, may adversely affect kidney health over time across populations with or at-risk for CKD [17].…”

Section: High Protein Diets May Be Harmful To Kidney Healthmentioning

confidence: 99%

“…Some health care providers, as well as patients, may express concerns that the carbohydrates burden of plant-dominant diets confounds dietary management of obesity, metabolic syndrome, or diabetes. However, different types of carbohydrates have different glycemic indices, and high protein or ketogenic diets, which may be recommended for these conditions, are associated with untoward consequences in disease and health [ 21 ]. Complex carbohydrates, including whole and minimally processed foods, are high in fiber and antioxidants and can reduce insulin resistance and improve glycemic control by a variety of biologically plausible mechanisms [ 147 ].…”

Section: Challenges and Pitfalls Of The Dietary Management Of Ckdmentioning

confidence: 99%

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Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

et al. 2020

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Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

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Section: High Protein Diets May Be Harmful To Kidney Healthmentioning

confidence: 99%

Section: Challenges and Pitfalls Of The Dietary Management Of Ckdmentioning

confidence: 99%

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

et al. 2020

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“…59,60 This was concordant with the findings in other studies where a significant increase of inflammation was detected after a very low carbohydrate diet intervention. 14,61 In this study, we observed that the serum levels of pro-oxidant molecules in KD fed diabetic mice were significantly higher than the HFD-fed diabetic mice (Figure 2A-C). This is in line with the previous study, which has demonstrated a significant increase in oxidative stress after KD intervention.…”

Section: Dovepressmentioning

confidence: 52%

<p>High-Intensity Interval Training Attenuates Ketogenic Diet-Induced Liver Fibrosis in Type 2 Diabetic Mice by Ameliorating TGF-β1/Smad Signaling</p>

Zhang¹,

Shen²,

Shen³

et al. 2020

DMSO

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Ketogenic diet (KD) and high-intensity interval training (HIIT) have preclinical benefits for type 2 diabetes (Db). However, the health risks of long-term KD use in diabetes should be ascertained and prevented. We hypothesized that KD-induced liver fibrosis in type 2 diabetic mice could be ameliorated by HIIT. Methods: Streptozotocin-induced type 2 diabetic mice were divided into high-fat diet (HFD) control (Db+HFD+Sed), KD control (Db+KD+Sed), HFD coupled with HIIT (Db +HFD+HIIT), and KD coupled with HIIT (Db+KD+HIIT) groups (n=6, per group). Control mice were kept in sedentary (Sed), while HIIT group mice underwent 40-minute highintensity interval training three alternate days per week. After 8-week intervention, the indicators of body weight and insulin resistance, oxidative stress markers, hepatic fibrosis, genetic and protein expression of related pathways were tested. Results: We found that fasting blood glucose level was reduced in the Db+HFD+HIIT, Db +KD+Sed, and Db+KD+HIIT groups. Insulin sensitivity was increased in diabetic mice of these groups, whereas ROS levels were decreased in mice that underwent HIIT. The immunohistochemical staining of liver, serum index, and hepatic parameters of diabetic mice in the KD group revealed liver fibrosis, which was significantly attenuated by HIIT. Besides, these effects of HIIT were the outcome of hepatic stellate cell's inactivation, reduced protein expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and the inhibition of TGF-β1/Smad signaling. Conclusion: KD had a profound fibrotic effect on the liver of type 2 diabetic mice, whereas HIIT ameliorated this effect. KD did not show any apparent benefit as far as glucose tolerance and homeostasis were concerned. Concisely, our results demonstrated that KD should be coupled with HIIT for the prevention and preclinical mitigation of type 2 diabetes.

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“…1, 11 Among the core components of the preventative strategies are nutritional and dietary intervention as featured in this been as effective for glycemic control or weight loss in randomized, controlled trials as often touted and may carry additional risks to long-term health. 21 Further, previous and emerging data (Table 1) suggest that high DPI in these diets, by way of causing increased intra-glomerular pressure with resultant glomerular hyperfiltration, may adversely affect kidney health over time across populations with or at-risk for CKD. 17…”

Section: The Burden Of Chronic Kidney Diseasementioning

confidence: 97%

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

Kalantar-Zadeh¹,

Joshi²,

Schlueter³

et al. 2020

Preprint

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Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

show abstract

The Ketogenic Diet for Obesity and Diabetes—Enthusiasm Outpaces Evidence

Cited by 100 publications

References 10 publications

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

<p>High-Intensity Interval Training Attenuates Ketogenic Diet-Induced Liver Fibrosis in Type 2 Diabetic Mice by Ameliorating TGF-β1/Smad Signaling</p>

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

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