The Metabolomic Landscape of Carbohydrate Restriction

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 30852

Special Issue Editor


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Guest Editor
Harvard Medical School, Boston, MA 02115, USA
Interests: obesity; diabetes; lipid metabolism; microbiome; nutrition; low-carbohydrate diets; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Carbohydrate-restricted and ketogenic diets are becoming increasingly popular not only for the management of obesity, diabetes, and epilepsy but also for many other chronic metabolic conditions. The myriad mechanisms through which carbohydrate restriction might be uniquely advantageous, or disadvantageous, for impacting states of health and disease deserves further exploration.

This Special Issue of Metabolites will publish reviews and original articles covering the latest developments on the effects of carbohydrate restriction on the metabolome and the physiological consequences. A short list of compounds that appear of particular interest to this area of research includes adiponectin, leptin, and other adipokines, apolipoproteins and lipids, angiopoietin-like proteins and another hepatocyte, fibroblast growth factors, and sex-hormone binding globulin, although this is by no means a comprehensive list.

We are open to receiving original human or animal research, case series, or review, perspective, and hypothesis manuscripts. All submissions should emphasize biological and metabolic mechanisms, and authors should attempt to delineate, not only what their work contributes to the literature, but also the boundaries of present knowledge on their topic and the important questions that remain to be answered. Given the mechanistic emphasis of this topic, 1 – 2 central guiding figures highlighting proposed mechanisms are encouraged.

Dr. Nicholas G. Norwitz
Guest Editor

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Keywords

  • carbohydrate-restriction
  • ketogenic diet
  • obesity
  • insulin
  • insulin resistance
  • lipoproteins
  • lipids
  • metabolome
  • adipokines
  • hepatokines

Published Papers (4 papers)

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17 pages, 2775 KiB  
Article
Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats
by Polina E. Nedoboy and Melissa M.-J. Farnham
Metabolites 2023, 13(1), 42; https://doi.org/10.3390/metabo13010042 - 27 Dec 2022
Cited by 1 | Viewed by 2555
Abstract
Hypoglycemia-associated autonomic failure (HAAF) is a serious, life-threatening complication of intensive insulin therapy, particularly in people with type 1 diabetes. The ketogenic diet is reported to beneficially affect glycemic control in people with type 1 diabetes, however its effects on the neurohormonal counterregulatory [...] Read more.
Hypoglycemia-associated autonomic failure (HAAF) is a serious, life-threatening complication of intensive insulin therapy, particularly in people with type 1 diabetes. The ketogenic diet is reported to beneficially affect glycemic control in people with type 1 diabetes, however its effects on the neurohormonal counterregulatory response to recurrent hypoglycemia and HAAF development are understudied. In this study we used Sprague Dawley rats to establish a HAAF model under non-diabetic and streptozotocin (STZ)-induced diabetic conditions and determined how nutritional ketosis affected the neurohormonal counterregulation and the activity of energy-sensing orexin (OX) neurons. We found that antecedent hypoglycemia diminished the sympathoexcitatory epinephrine response to subsequent hypoglycemia in chow-fed non-diabetic rats, but this did not occur in STZ-diabetic animals. In all cases a ketogenic diet preserved the epinephrine response. Contrary to expectations, STZ-diabetic keto-fed rats showed reduced OX activity in the recurrent hypoglycemia group, which did not occur in any other group. It is possible that the reduced activation of OX neurons is an adaptation aimed at energy conservation accompanied by diminished arousal and exploratory behaviour. Our data suggests that while a ketogenic diet has beneficial effects on glycemia, and epinephrine response, the reduced activation of OX neurons could be detrimental and warrants further investigation. Full article
(This article belongs to the Special Issue The Metabolomic Landscape of Carbohydrate Restriction)
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18 pages, 1500 KiB  
Article
A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice
by Erin R. Saito, Cali E. Warren, Cameron M. Hanegan, John G. Larsen, Johannes D. du Randt, Mio Cannon, Jeremy Y. Saito, Rachel J. Campbell, Colin M. Kemberling, Gavin S. Miller, Jeffrey G. Edwards and Benjamin T. Bikman
Metabolites 2022, 12(11), 1019; https://doi.org/10.3390/metabo12111019 - 25 Oct 2022
Cited by 8 | Viewed by 7618
Abstract
Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer’s disease and major depressive disorder. However, [...] Read more.
Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer’s disease and major depressive disorder. However, their effects on cognitive function in healthy individuals is less established. Here, we explored the mitochondrial and performative outcomes of a novel eight-week ketone-supplemented ketogenic (KETO) diet in healthy adult male and female mice. In a novel object recognition test, KETO mice spent more time with the novel, compared to familiar, object, indicating an improvement in recognition memory. High-resolution respirometry on permeabilized hippocampal tissue returned significant reductions in mitochondrial O2 consumption. No changes in ATP production were observed, yielding a significantly higher ATP:O2 ratio, a measure of mitochondrial efficiency. Together, these findings demonstrate the KETO diet improves hippocampal mitochondrial efficiency. They add to a growing body of evidence that suggests ketones and ketogenic diets are neuroprotective and metabolically and cognitively relevant, even in healthy adults. They also suggest that ketogenic lifestyle changes may be effective strategies for protecting against cognitive decline associated with aging and disease. Full article
(This article belongs to the Special Issue The Metabolomic Landscape of Carbohydrate Restriction)
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8 pages, 419 KiB  
Article
A Company Is Only as Healthy as Its Workers: A 6-Month Metabolic Health Management Pilot Program Improves Employee Health and Contributes to Cost Savings
by Nicholas G. Norwitz, Adrian Soto-Mota and Tro Kalayjian
Metabolites 2022, 12(9), 848; https://doi.org/10.3390/metabo12090848 - 9 Sep 2022
Cited by 3 | Viewed by 11240
Abstract
Chronic diet-related metabolic diseases, including diabetes and obesity, impose enormous burdens on patient wellness, healthcare costs, and worker productivity. Given the interdependent nature of the human and economic costs of metabolic disease, companies should be incentivized to invest in the health of their [...] Read more.
Chronic diet-related metabolic diseases, including diabetes and obesity, impose enormous burdens on patient wellness, healthcare costs, and worker productivity. Given the interdependent nature of the human and economic costs of metabolic disease, companies should be incentivized to invest in the health of their workforce. We report data from an ongoing pilot program in which employees of a manufacturing company with obesity, prediabetes, or diabetes are being treated by a metabolic health clinic using a carbohydrate restriction, community-orientated telemedicine approach. 10 patients completed the first 6 months of the program, and all lost weight, with a mean weight reduction of 38.4 lbs (17.4 kg). Improvements in HbA1c, fasting glucose, HOMA-IR, triglycerides, C-reactive protein, and systolic blood pressure were also observed across the group. Furthermore, the 10-year risk of having a major cardiovascular event, as calculated by the American Heart Association risk calculator, decreased from a mean of 9.22 to 5.18%, representing a 44% relative risk reduction. As a result of improvements in their metabolic health, patients were able to discontinue medications, leading to an estimated annualized cost savings of USD 45,171.70. These preliminary data provide proof-of-principle that when companies invest in the metabolic health of their workers, both parties stand to gain. Full article
(This article belongs to the Special Issue The Metabolomic Landscape of Carbohydrate Restriction)
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10 pages, 1507 KiB  
Case Report
Ketogenic Diet Initially Masks Symptoms of Hypercortisolism in Cushing’s Disease
by Mary Kimberly Dugandzic, Esther-Carine Pierre-Michel and Tro Kalayjian
Metabolites 2022, 12(11), 1033; https://doi.org/10.3390/metabo12111033 - 28 Oct 2022
Cited by 2 | Viewed by 7629
Abstract
Cushing’s syndrome (CS) is a diagnosis used to describe multiple causes of serum hypercortisolism. Cushing’s disease (CD), the most common endogenous subtype of CS, is characterized by hypercortisolism due to a pituitary tumor secreting adrenocorticotropic hormone (ACTH). A variety of tests are used [...] Read more.
Cushing’s syndrome (CS) is a diagnosis used to describe multiple causes of serum hypercortisolism. Cushing’s disease (CD), the most common endogenous subtype of CS, is characterized by hypercortisolism due to a pituitary tumor secreting adrenocorticotropic hormone (ACTH). A variety of tests are used to diagnose and differentiate between CD and CS. Hypercortisolism has been found to cause many metabolic abnormalities including hypertension, hyperlipidemia, impaired glucose tolerance, and central adiposity. Literature shows that many of the symptoms of hypercortisolism can improve with a low carb (LC) diet, which consists of consuming <30 g of total carbohydrates per day. Here, we describe the case of a patient with CD who presented with obesity, hypertension, striae and bruising, who initially improved some of his symptoms by implementing a LC diet. Ultimately, as his symptoms persisted, a diagnosis of CD was made. It is imperative that practitioners realize that diseases typically associated with poor lifestyle choices, like obesity and hypertension, can often have alternative causes. The goal of this case report is to provide insight on the efficacy of nutrition, specifically a LC diet, on reducing metabolic derangements associated with CD. Additionally, we will discuss the importance of maintaining a high index of suspicion for CD, especially in those with resistant hypertension, obesity and pre-diabetes/diabetes. Full article
(This article belongs to the Special Issue The Metabolomic Landscape of Carbohydrate Restriction)
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