Apologies if this is off-topic, but I was making some posts on r/keto, based on what I thought was solid scientific evidence. Basically, my understanding is that high protein interferes with ketosis.

I'm wondering if there have been more recent studies that contract the ones I've read, of if the r/keto moderators are pulling these "facts" out of their ***. From what I can see, it seems like they are contradicting both my personal experience with keto and also the only studies on this topic that I was able to find.

The sources in the Faq seem mostly like books, I don't really see studies or citations for these.

I'm attaching some screenshots of my interaction.

https://preview.redd.it/hdyxrmu7anzc1.png?width=1213&format=png&auto=webp&s=ba40a1c14b0753d805e056cf46d035e465d71977

https://preview.redd.it/46qbihv7anzc1.png?width=1209&format=png&auto=webp&s=3a437471a33cac70c30448c6af28180a473a966c

https://preview.redd.it/8uzyofv7anzc1.png?width=1237&format=png&auto=webp&s=59f292da72786f37acf2c7243164617e2404a7da

https://preview.redd.it/41aj6fv7anzc1.png?width=1216&format=png&auto=webp&s=5e246ebbbf22af05a4ae17f048c52c654c9f1def

https://preview.redd.it/b75yoiu7anzc1.png?width=1426&format=png&auto=webp&s=14c07981930b7161c4a769f21d72e82e9eb8b9b8

I did Keto for 5 years from 2017 to December 2022.

I had to stop in December because my body was releasing it’s sodium at an abnormal rate and it’s gotten worse since then.

Even today as I eat a carb diet, my sodium needs are abnormally high. 15k -20k a day even with proper electrolyte supplementation.

I’ve been to the doctor numerous times, my blood work and kidneys are normal. Everything is normal. The doctors are confused as to what is causing this excessive dehydration.

Sipping electrolytes only mildly helps, I need to actually eat electrolyte dense food to hydrate myself. If I don’t consume that much sodium, I feel dry, dehydrated and Keto Flu symptoms like insomnia, moodiness, anxiety etc. come.

I’m assuming food helps because the insulin helps to push the electrolytes into my body…?

From what I understand, low insulin is what causes our bodies to release sodium. I’ve noticed when I fast (skip breakfast) the dehydration is much worse. Fasting all day is pretty much impossible or I’d feel super dry, dehydrated, and terrible.

Eating 3 meals a day seems to help with feeling more hydrated.

So it has to be insulin related right? One of my kidney doctors said maybe the excess sodium intake is what is making my body excrete so much of it… but if I don’t take in that much I get Keto flu symptoms so how would I even fix it 🤣

I think what caused this was I was fasting for 8 months, eating 1 meal a day. I was only supplementing sodium (a few cups of broth a day) and magnesium. No potassium except what I got from food… everything was fine until I did that. I think that threw my electrolytes out of wack.

The dehydration slowly got worse, slowly needing more and more broth every day before my meal but I wasn’t realizing it at the time.

Low carb and fasting create a diuretic effect… maybe if I do the opposite, eat every 3 hrs and spike insulin often. Maybe I can slowly tell my body to stop releasing so much sodium?

I haven’t encountered anyone else that has this problem even though I’ve googled it many times.

Anyone have any ideas on what could be causing an excessive diuretic effect and how could I go about reversing it because my labs have all come back normal numerous times…

https://www.mdpi.com/2073-4409/13/9/784

Abstract

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.

https://www.sciencedirect.com/science/article/abs/pii/S1551741124001517

Abstract

Background

Acute respiratory distress syndrome (ARDS) is a lung complication of COVID-19 that requires intensive care and ventilation. Beta-hydroxybutyrate (BHB) is a ketone body that can modulate metabolism and inflammation in immune cells and lung tissues. We hypothesized that oral BHB could alleviate COVID-19 related ARDS by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines.

Methods

We randomized 75 patients with mild (as per Berlin criteria) ARDS symptoms to receive oral 25 g twice daily or placebo for five days. The primary outcome was the change in pro-inflammatory cytokines (Interleukin-1β, Interleukin-6, interleukin-18, tumour necrosis factor-alpha) and anti-inflammatory cytokine (interleukin-10) from baseline to day 5. The secondary outcomes were the change in BHB levels from baseline to day 5, the number of hospitalization days, and the occurrence of adverse events.

Results

Treatment with formulated BHB resulted in a significant decrease in pro-inflammatory cytokines; Interleukin-1β (p=0.0204), Interleukin-6 (p=0.0309), interleukin-18 (p=0.0116), tumour necrosis factor-alpha (p=0.0489) and increase in interleukin-10 (p=0.0246) compared treatment with placebo. Importantly, higher BHB levels (p=0.0001) were observed after supplementation; additionally, patients who underwent this approach were hospitalized for fewer days. No serious adverse events were reported.

Conclusion

Beta-hydroxybutyrate, an oral adjunct therapy, has shown promising results in ameliorating symptoms of ARDS. This includes reduced inflammation, oxidative stress, and decreased patient fatigue levels. Further study with a large sample size is warranted to assess the potential of BHB therapy's effectiveness in reducing the development of severe illness.

https://aacrjournals.org/cancerres/article/84/9_Supplement/PO3-02-03/744313

Abstract

Obesity is associated with an increased risk of breast cancer recurrence, similar in magnitude to the reduction in risk seen with the use of adjuvant chemotherapy. However, whether and how obesity causes that increased risk of recurrence remains unknown. Plausible mechanisms include obesity-mediated increases in estrogen signaling, inflammatory conditions resulting from obesity, or effects on insulin or other growth factor signaling pathways resulting from the insulin-resistant state that often accompanies obesity. While phosphatidyl inositol 3-kinase (PI3K) signaling is the normal, biological effector of insulin signaling, abnormal activation of PI3K is of particular concern in breast cancer, where it is associated with resistance to endocrine therapies and HER2-targeted therapies.

We hypothesize that at least part of the adverse outcome associated with obesity results from aberrant activation of PI3K signaling in tumors. This may confer resistance to established therapies, or directly stimulate tumor growth (particularly in tumors with existing PI3K pathway mutations), or both. We tested a dietary intervention designed to alter insulin resistance pathophysiology coupled with endocrine therapy in the well-established neoadjuvant treatment paradigm in breast cancer. This will allow us to study the effects of the dietary intervention directly on tumor biology.

The primary objective of this neoadjuvant study was to assess feasibility and tolerability of 2 weeks of a very low-carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+ disease. Up to 36 patients will be enrolled for this pilot and feasibility study (24 in the treatment group and 12 controls). Baseline metabolic parameters will be measured and the treatment group will begin a dietitian-supervised 2-week diet to induce a ketogenic state, along with letrozole 2.5 mg daily. The control group will receive only letrozole. At the end of 2 weeks, patients will proceed with surgical treatment of their breast cancer. We will report the primary outcome measure of feasibility, assessed by determining 1) the proportion of patients in the diet group achieving ketosis, 2) adherence to the diet and 3) participant-reported measures of stress, fatigue, and emotional health. For both groups, cell proliferation will be measured in a tumor biopsy obtained from the surgical specimen and compared with the pre-treatment diagnostic biopsy. Correlative studies will evaluate tumor markers of insulin/PI3K signaling before and after the intervention and between diet and control.

https://doi.org/10.20960/nh.05171

https://pubpeer.com/search?q=10.20960/nh.05171

Fourteenth Jesús Culebras Lecture. Ketogenic diet, a half-discovered treatment

Abstract

The ketogenic diet was an amazing approach to treating epilepsy from its beginning. The body undergoes a change in obtaining energy, going from depending on carbohydrates to depending on fats, and then a whole series of biochemical routes are launched that, independently but also complementary, give rise to a set of effects that benefit the patient. This search for its mechanism of action, of devising how to improve compliance and take advantage of it for other diseases has marked its trajectory. This article briefly reviews these aspects, emphasizing the importance of continuing to carry out basic and clinical research so that this treatment can be applied with solid scientific bases.

------------------------------------------ Info ------------------------------------------

Open Access: True (not always correct)

Authors:

• Consuelo Carmen Pedrón Giner

Additional links:

• https://doi.org/10.20960/nh.05171

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

WARNING Preprint! Not peer-reviewed!

https://www.biorxiv.org/content/10.1101/2024.05.03.24306699

Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults, a randomized, parallel arm, double-blind, placebo-controlled, pilot study.

Abstract

Objectives: Ketone bodies are endogenous metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to determine tolerability and safety of KE ingestion in older adults. Design: Randomized, placebo-controlled, double-blinded, parallel-arm trial, with a 12-week intervention period (NCT05585762). Setting: General community, Northern California, USA. Participants: Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n=30) were randomized and n=23 (M= 14, F=9) completed the protocol. Intervention: Participants were randomly allocated to consume either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil. Measurements: Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events. Results: There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n =2 (14.3% [90% CI = 2.6 - 38.5]), PLA n=1 (7.1% [90% CI = 0.4 - 29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks, symptoms were reported less frequently between 2 - 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group. Conclusions: This KE was safe and well-tolerated in healthy older adults. These results provide a foundation for use of KEs in aging research.

##Authors:

Stubbs, B. J., Stephens, E. B., Senaheera, C., Peralta, S., Roa Diaz, S., Alexander, L., Silverman Martin, W., Garcia, T. Y., Yukawa, M., Morris, J., Blonquist, T. M., Johnson, J. B., Newman, J. C.

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://doi.org/10.1016/j.bbadis.2024.167210

https://pubpeer.com/search?q=10.1016/j.bbadis.2024.167210

https://pubmed.ncbi.nlm.nih.gov/38704001

Abstract

Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

##Authors:

• Jiang H
• Zeng Y
• Jiang X
• Xu X
• Zhao L
• Yuan X
• Xu J
• Zhao M
• Wu F
• Li G

------------------------------------------ Info ------------------------------------------

Open Access: False

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://doi.org/10.1152/ajpcell.00718.2023

https://pubpeer.com/search?q=10.1152/ajpcell.00718.2023

https://pubmed.ncbi.nlm.nih.gov/38708524

Abstract

Ketone bodies (acetoacetate and β-hydroxybutyrate) are oxidized in skeletal muscle mainly during fasting as an alternative source of energy to glucose. Prior studies suggest that there is a negative relationship between increased muscle ketolysis and muscle glucose metabolism in mice with obesity and/or type 2 diabetes. Therefore, we investigated the connection between increased ketone body exposure and muscle glucose metabolism by measuring the effect of a 3-hour exposure to ketone bodies on glucose uptake in differentiated L6 myotubes. We showed that exposure to acetoacetate at a typical concentration (0.2 mM) resulted in increased basal glucose uptake in L6 myotubes, which was dependent on increased membrane GLUT4 translocation. Basal and insulin-stimulated glucose uptake was also increased with a concentration of acetoacetate reflective of diabetic ketoacidosis or a ketogenic diet (1 mM). We found that β-hydroxybutyrate had a variable effect on basal glucose uptake, in that a racemic mixture of the two β-hydroxybutyrate enantiomers (D and L) appeared to decrease basal glucose uptake, while 3 mM D-β-hydroxybutyrate alone increased basal glucose uptake. However, the effects of the ketone bodies individually were not observed when acetoacetate was present in combination with β-hydroxybutyrate. These results provide insight that will help elucidate the effect of ketone bodies in the context of specific metabolic diseases and nutritional states (e.g., type 2 diabetes and ketogenic diets).

##Authors:

• Khouri H
• Roberge M
• Ussher JR
• Aguer C

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

Hello all,

Have a question regarding gluconeogenesis and metformin. Non diabetic but insulin resistant

Basically- I didn't realise that ketones don't become your fuel source until 'fat adapted' and took metformin to see if it helps with my insulin resistance (reason for keto diet).

Metformin inhibits gluconeogenesis- protein and fat conversion to glucose in liver!

To my surprise, it made me very sleepy, and actually able to sleep. I've had very consistent energy on keto (1.5 weeks in) and struggled massively to sleep.

I took it again today, and now I feel like shit- almost like a carb high/low.

Is it dangerous using metformin since it will inhibit gluconeogenesis- and will it be safe to reintroduce once running on ketones? Because it technically inhibits my main source of glucose production/energy until ketones take over...

As well- it increases blood ketones and can cause acidosis- am I at risk of this now?

Or is this ok since non diabetic?

I only used 500mg.

Thanks

https://www.tandfonline.com/doi/full/10.1080/00015385.2018.1510801

Abstract

Background:

High-sensitive cardiac troponin (hsTn) levels can be elevated due to non-pathological events such as strenuous exercise. However, the effect of statins on circulating hsTnT levels with moderate exercise is uncertain. Therefore, we evaluated the impact of statins on hsTnT level with moderate exercise.

Methods:

We enrolled a total of 56 patients: 26 statin users and 30 non-users. All patients were shown to have no coronary artery disease before participating in the study. Participants performed a fixed-protocol moderate level exercise. HsTnT levels were measured before and 4 h after the exercise. Participants were also grouped based on their hsTnT levels, as proposed in the recent European Society of Cardiology guideline (0-1 hour algorithm) for acute coronary syndromes without persistent ST-segment elevation.

Results:

Statin users showed a significant increase in serum hsTnT levels with moderate exercise (p = .004), whereas the control group showed a modest increase without statistical significance (p = .664). The percentage of patients whose hsTnT levels exceeded the rule-out limits for non-ST-segment myocardial infarction diagnosis (according to the 0-1 algorithm) after moderate exercise varied significantly between groups (p = .024).

Conclusions:

Statin therapy can cause a significant increase in hsTnT levels after moderate exercise. This increase can jeopardise the accuracy of clinical diagnoses based on the newly implemented algorithms. The awareness of these adverse effects of statins, mainly used by patients with high risk of coronary events, can prevent misdiagnosis or unnecessary hospitalisations.

https://www.cell.com/cell/abstract/S0092-8674(24)00226-5

Highlights

• Cholesin is a cholesterol-induced gut hormone • Cholesin regulates plasma cholesterol levels in both human and mouse • Cholesin inhibits PKA-ERK1/2 signaling via binding to GPR146 • Cholesin suppresses SREBP2-controlled cholesterol synthesis in the liver

Summary

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

https://www.frontiersin.org/articles/10.3389/fncel.2024.1409717/abstract

Mitochondrial homeostasis includes balancing organelle biogenesis with recycling (mitophagy). The ketogenic diet protects retinal ganglion cells (RGCs) from glaucomaassociated neurodegeneration, with a concomitant increase in mitochondrial biogenesis. This study aimed to determine if the ketogenic diet also promoted mitophagy. MitoQC mice that carry a pH-sensitive mCherry-GFP tag on the outer mitochondrial membrane were placed on a ketogenic diet or standard rodent chow for 5 weeks; ocular hypertension (OHT) was induced via magnetic microbead injection in a subset of control or ketogenic diet animals one week after the diet began. As a measure of mitophagy, mitolysosomes were quantified in sectioned retina immunolabeled with RBPMS for RGCs or vimentin for Müller glia. Mitolysosomes were significantly increased as a result of OHT and the ketogenic diet (KD) in RGCs. Interestingly, the ketogenic diet increased mitolysosome number significantly higher than OHT alone. In contrast, OHT and the ketogenic diet both increased mitolysosome number in Müller glia to a similar degree. To understand if hypoxia could be a stimulus for mitophagy, we quantified mitolysosomes after acute OHT, finding significantly greater mitolysosome number in cells positive for pimonidazole, an adduct formed in cells exposed to hypoxia. Retinal protein analysis for BNIP3 and NIX showed no differences across groups, suggesting that these receptors were equivocal for mitophagy in this model of OHT. Our data indicates that OHT and hypoxia stimulate mitophagy and that the ketogenic diet was additive for mitophagy in RGCs. The different response across RGCs and Müller glia to the ketogenic diet may reflect the different metabolic needs of these cell types.

https://doi.org/10.23736/S2724-5276.21.05923-1

https://pubpeer.com/search?q=10.23736/S2724-5276.21.05923-1

Novel insight into GLUT1 deficiency syndrome: screening for emotional and behavioral problems in youths following ketogenic diet

Abstract

BACKGROUND

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare disorder with a broad spectrum of neurological manifestations. The ketogenic diet (KD) is, to date, the gold standard treatment. Behavioral problems, well recognized in patients with chronic conditions, have not been, so far, deeply investigated in GLUT1DS patients. We performed an exploratory study to assess the risk of emotional and behavioral problems and investigated the potential role of influencing factors related to the pathology itself or KD treatment.

METHODS

This was a mono-center retrospective study involving youths with GLUT1Ds treated with KD and a group of migraine patients age- and gender-matched. Patients were included if the main caregiver completed the Child Behavior Check List 6-18 (CBCL). Descriptive statistics for demographic and clinical data and questionnaire scores were computed. Correlational analyses were used to assess the potential associations of clinical variables and age and time from KD introduction with CBCL scores in GLUT1DS patients.

RESULTS

We enrolled nine youths with GLUT1DS and 9 with migraine. In the GLUT1DS group, none of the mean scores of the CBCL items fell within the borderline/clinical range, except for social problems located in the borderline range. Investigation for influencing factors revealed the patient's age related to withdrawn/depressive (r=0.709, P=0.032) and social problems (r=.684, P=0.042). Time from the introduction of KD was related to social problems (r=.827, P=0.006). From the comparison with the scores obtained from migraine patients, significantly higher scores emerged in the latter group in internalizing problems (Z=-2.48, P=0.01), externalizing problems (Z=-3.49, P<0.001), anxious/depressed subscale (Z=-2.37, P=0.014), somatic complaints subscale (Z=-2.624, P=0.008), aggressive behavior subscale (Z=-2.539, P=0.011).

CONCLUSIONS

Although highly exploratory in its nature, this study provides a novel insight into GLUT1DS. Our data suggested that the risk for internalizing problems in GLUT1DS youths was related to higher age and higher time elapsed from KD introduction. They occurred at a sub-clinical level, making them difficult to detect, if not expressly and systematically investigated.

------------------------------------------ Info ------------------------------------------

Open Access: False (not always correct)

Authors:

• Costanza VARESIO
• Martina P. ZANABONI
• Ludovica PASCA
• Livio PROVENZI
• Cinzia FERRARIS
• Anna TAGLIABUE
• Elena PEZZOTTI
• Adriana CARPANI
• Pierangelo VEGGIOTTI
• Valentina DE GIORGIS

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://doi.org/10.1007/s40618-024-02364-9

https://pubpeer.com/search?q=10.1007/s40618-024-02364-9

https://pubmed.ncbi.nlm.nih.gov/38696124

Abstract

##PURPOSE

Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS).

##METHODS

EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months.

##RESULTS

It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS.

##CONCLUSION

The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

##Authors:

• Fernandez-Pombo A
• Lorenzo PM
• Carreira MC
• Gomez-Arbelaez D
• Castro AI
• Primo D
• Rodriguez J
• Sajoux I
• Baltar J
• de Luis D
• Bellido D
• Crujeiras AB
• Casanueva FF

------------------------------------------ Info ------------------------------------------

Open Access: False

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://doi.org/10.1111/dom.15641

https://pubpeer.com/search?q=10.1111/dom.15641

https://pubmed.ncbi.nlm.nih.gov/38699792

Abstract

##AIM

To examine the effects of the thiazolidinedione (TZD) pioglitazone on reducing ketone bodies in non-obese patients with T2DM treated with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin.

##METHODS

Crossover trials with two periods, each treatment period lasting 4 weeks, with a 4-week washout period, were conducted. Participants were randomly assigned in a 1:1 ratio to receive pioglitazone combined with canagliflozin (PIOG   CANA group) versus canagliflozin monotherapy (CANA group). The primary outcome was change (Δ) in β-hydroxybutyric acid (β-HBA) before and after the CANA or PIOG   CANA treatments. The secondary outcomes were Δchanges in serum acetoacetate and acetone, the rate of conversion into urinary ketones, and Δchanges in factors related to SGLT2 inhibitor-induced ketone body production including non-esterified fatty acids (NEFAs), glucagon, glucagon to insulin ratio, and noradrenaline (NA). Analyses were performed in accordance with the intention-to-treat principle.

##RESULTS

Twenty-five patients with a mean age of 49 ± 7.97 years and a body mass index of 25.35 ± 2.22 kg/m^(2) were included. One patient discontinued the study during the washout period. Analyses revealed a significant increase in the levels of serum ketone bodies and an elevation in the rate of conversion into urinary ketones after both interventions. However, differernces in levels of ketone bodies (except for acetoacetate) in the PIOG   CANA group were significantly smaller than in the CANA group (219.84 ± 80.21 μmol/L vs. 317.69 ± 83.07 μmol/L, p < 0.001 in β-HBA, 8.98 ± 4.17 μmol/L vs. 12.29 ± 5.27 μmol/L, p = 0.018 in acetone). NEFA, glucagon, glucagon to insulin ratio, and NA were also significantly increased after both CANA and PIOG   CANA treatments, while only NEFAs demonstrated a significant difference between the two groups. Correlation analyses revealed a significant association between the difference in Δchanges in serum NEFA levels with the differences in Δchanges in ketones of β-HBA and acetoacetate.

##CONCLUSION

Supplementation of pioglitazone could alleviate canagliflozin-induced ketone bodies. This benefit may be closely associated with decreased substrate NEFAs rather than other factors including glucagon, fasting insulin and NA.

##Authors:

• Yang M
• Yue H
• Xu Q
• Shao S
• Chen Y

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://knightscholar.geneseo.edu/great-day-symposium/great-day-2024/posters-2024/88/

Abstract

The ketogenic diet (KD) has long been used to control epilepsy, but more recently has also been shown to improve symptoms of Autism Spectrum Disorder (ASD). ASD is a highly prevalent disorder, characterized partially by repetitive behavior. Genetics, environmental conditions, and resultant injury to the brain, have been linked to an increased risk for ASD. KD is thought to work as an anti-inflammatory and has been shown to decrease repetitive behavior in a mouse model of ASD; but, how KD works within ASD is not well understood. This project works with a mouse model of ASD to determine if early KD intervention prevents the development of ASD behaviors in mice, and explores if glial fibrillary acidic protein (GFAP), a marker of inflammation, may be how KD helps ASD. It is hypothesized that mice that develop repetitive behavior will show altered expression of GFAP that will be restored by KD intervention.

https://knightscholar.geneseo.edu/great-day-symposium/great-day-2024/posters-2024/81/

Abstract

Ketogenic diet (KD) is a diet with high fat, moderate amount of protein and low carbohydrate. KD has been known for many therapeutic purposes, including alcohol abuse. This project focuses on how KD affects cognitive performance in mice administered alcohol. Three groups of mice were used in this study; one group was given 20% EtOH and KD, another group with only 20% EtOH, and the last group without 20% EtOH or KD which was our control group. Before the alcohol administration period began, the KD mice were fed KD for 1 week. Then, mice assigned to EtOH groups were injected intraperitoneally for 10 days in a row, and no-alcohol controls were injected with 0.1mL saline. We found that mice fed KD performed better in a test of working memory. Alcohol moderately increased latencies in the maze and beams broken in a locomotor test. No differences were found in the hippocampus following a stain that shows cell bodies.

https://knightscholar.geneseo.edu/great-day-symposium/great-day-2024/posters-2024/34/

Abstract

Impaired social interaction is one of three key diagnostic criteria for Autism Spectrum Disorder (ASD). Other criteria for ASD include repetitive behavior and impaired communication skills. The prevalence of this developmental condition is increasing within the United States, yet no cure is currently available. The ketogenic diet (KD) is a high fat, low carb diet that can help many neurological issues in humans, such as epilepsy. This study investigates the effects of KD on social and repetitive behavior using an inbred mouse model genetically predisposed to developing stereotypic behaviors, specifically, repetitive circling. We compared locomotor and social behaviors of older male FVB mice fed KD or standard lab chow. Although we hypothesized that three weeks of KD would increase social interaction and decrease repetitive behavior, we did not find significant effects of KD on behavior in this cohort of mice. To investigate neurobiological changes associated with KD, we compared the expression of cell bodies, astrocytes, and dopamine 2 receptor proteins in the dorsolateral striatum, which is important in movement selection. Because stereotypic mice circle in a preferred direction, we also checked for differences between the contralateral and ipsilateral hemispheres.

https://journalofmetabolichealth.org/index.php/jmh/article/view/93

Abstract

The use of therapeutic carbohydrate restriction (TCR) in the form of a ketogenic diet (KD) in neurodegenerative disorders such as Parkinson’s disease (PD) is increasing as an alternative treatment for primary and secondary symptoms. There exists a gap in the literature on symptoms of PD in the setting of metabolic syndrome (MetSyn) and possible comorbid impact on symptoms, biomarkers of health, cardiac risk, depression and anxiety. This case report documents a 24-week KD intervention for a 53-year-old man with multiple comorbid diagnoses, PD (Hoehn-Yahr stage IIa) with a history of morbid obesity with increased waist circumference, prediabetes, hyperinsulinaemia and significantly impaired mobility with chronic back pain, anxiety disorder and depression. Baseline cardiac risk ratios (CRR = triglycerides/HDL) were calculated and compared. The KD approach involved a well-formulated, ketogenic diet (fats 70%; protein 25%; carbohydrates 5% according to total daily energy intake for 24 weeks). Baseline, 12-week and 24-week biomarkers and scores on scales were compared. Clinically significant results were found when baseline biomarker results and scales were compared with 12-week results. Positive trends were seen for all variables at 24 weeks. Improvements in health biomarkers, including HbA1C, high sensitivity C-reactive protein (hs-CRP), triglycerides, fasting insulin, weight loss, waist circumference and cardiac risk were observed at 12 and 24 weeks. Some improvements in scores on an anxiety scale were seen. Based on our findings, KD is safe and effective for improving health biomarkers and symptoms of MetSyn, depression, anxiety and symptoms of PD. Future clinical trial studies for more generalisable results are needed.

https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1344891/abstract

Abstract

Introduction:

Clear cell renal cell carcinoma (ccRCC) is characterized by a predominant metabolic reprogramming triggering energy production by anaerobic glycolysis at the expense of oxydative phosphorylation. Ketogenic diet (KD), which consists of high fat and low carbohydrate intake, could bring required energy substrates to healthy cells while depriving tumor cells of glucose. Our objective was to evaluate the effect of KD on renal cancer cell tumor metabolism and growth proliferation.

Methods:

Growth cell proliferation and mitochondrial metabolism of ACHN and RENCA renal carcinoma cells were evaluated under ketone bodies (KB) exposure. In vivo studies were performed with mice (nude or Balb/c) receiving a xenograft of ACHN cells or RENCA cells, respectively, and were then split into 2 feeding groups, fed either with standard diet or a 2:1 KD ad libitum. To test the effect of KD associated to immunotherapy, Balb/c mice were treated with anti-PDL1 mAb. Tumor growth was monitored.

Results:

In vitro, KB exposure was associated with a significant reduction of ACHN and RENCA cell proliferation and viability, while increasing mitochondrial metabolism. In mice, KD was associated with tumor growth reduction and PDL-1 gene expression up-regulation. In Balb/c mice adjuvant KD was associated to a better response to anti-PDL-1 mAb treatment.

Conclusions.

KB reduced the renal tumor cell growth proliferation and improved mitochondrial respiration and biogenesis. KD also slowed down tumor growth of ACHN and RENCA in vivo. We observed that PDL-1 was significantly overexpressed in tumor in mice under KD. Response to anti-PDL-1 mAb was improved in mice under KD. Further studies are needed to confirm the therapeutic benefit of adjuvant KD combined with immunotherapy in patients with kidney cancer.

https://doi.org/10.1007/s40496-024-00376-1

https://pubpeer.com/search?q=10.1007/s40496-024-00376-1

Ketogenic Diets Hold Therapeutic Potential Against Periodontal Inflammation

Abstract

Purpose of Review Periodontitis, one of the most prevalent diseases in the world, is caused by the accumulation of dysbiotic microbial biofilm on the teeth leading to chronic inflammation of the tissues surrounding the teeth. Type 2 diabetes mellitus (T2DM), obesity, chronic stress, and smoking are some of the risk factors for the disease. A high-carbohydrate diet also increases the risk of periodontal inflammation. Modifying diet and nutrition could serve as a preventive and therapeutic tool to target multiple risk factors simultaneously. Recent Findings Emerging evidence shows that the ketogenic diet induces hormetic stress and switches on various cell-protective anti-inflammatory and antioxidant mechanisms. The ketogenic diet also improves mitochondrial function, DNA repair, and autophagy. The diet can effectively treat periodontitis risk factors such as T2DM and obesity. By restricting carbohydrates, the diet improves glycaemic control in T2DM patients and can effectively produce fat loss and reduce BMI (body-mass index) in obese patients. Poor long-term compliance and high cost are the drawbacks of the diet and the potential of the diet to increase cardiovascular disease risk needs further investigation. Summary Taken together, ketogenic diets, through various mechanisms reduce inflammation, mitigate oxidative stress, improve metabolic health, and can be used as a therapeutic tool to treat periodontal inflammation. Since robust scientific evidence for the ketogenic diet is currently scarce, future research should study the diet's efficacy, effectiveness, and safety in managing periodontal inflammation.

------------------------------------------ Info ------------------------------------------

Open Access: True (not always correct)

Authors:

• Shaswata Karmakar
• Shivaprasad
• Ramya Arangaraju
• Baishakhi Modak
• Shashikiran Shanmugasundaram

Additional links:

• https://doi.org/10.1007/s40496-024-00376-1

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://www.mdpi.com/2072-6643/16/9/1348

Abstract

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets influences intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate−dextran (FITC–dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC–dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.

https://doi.org/10.1111/dmcn.15928

https://pubpeer.com/search?q=10.1111/dmcn.15928

https://pubmed.ncbi.nlm.nih.gov/38669468

Abstract

Ketogenic diet therapy (KDT) is a safe and effective treatment for epilepsy and glucose transporter type 1 (GLUT1) deficiency syndrome in infancy. Complete weaning from breastfeeding is not required to implement KDT, however, breastfeeding remains uncommon. Barriers include feasibility concerns and lack of referrals to expert centres. Therefore, practical strategies are needed to help mothers and professionals overcome these barriers and facilitate the inclusion of breastfeeding and human milk during KDT. A multidisciplinary expert panel met online to address clinical concerns, systematically reviewed the literature, and conducted two international surveys to develop an expert consensus of practical recommendations for including human milk and breastfeeding in KDT. The need to educate about the nutritional benefits of human milk and to increase breastfeeding rates is emphasized. Prospective real-world registries could help to collect data on the implementation of breastfeeding and the use of human milk in KDT, while systematically including non-seizure-related outcomes, such as quality of life, and social and emotional well-being, which could improve outcomes for infants and mothers.

##Authors:

• van der Louw E
• Trimmel-Schwahofer P
• Devlin A
• Armeno M
• Thompson L
• Cross JH
• Auvin S
• Dressler A

------------------------------------------ Info ------------------------------------------

Open Access: True

Additional links:

• https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dmcn.15928

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF

https://doi.org/10.3390/nu16081213

https://pubpeer.com/search?q=10.3390/nu16081213

https://pubmed.ncbi.nlm.nih.gov/38674903

Abstract

It is widely acknowledged that the ketogenic diet (KD) has positive physiological effects as well as therapeutic benefits, particularly in the treatment of chronic diseases. Maintaining nutritional ketosis is of utmost importance in the KD, as it provides numerous health advantages such as an enhanced lipid profile, heightened insulin sensitivity, decreased blood glucose levels, and the modulation of diverse neurotransmitters. Nevertheless, the integration of the KD with pharmacotherapeutic regimens necessitates careful consideration. Due to changes in their absorption, distribution, metabolism, or elimination, the KD can impact the pharmacokinetics of various medications, including anti-diabetic, anti-epileptic, and cardiovascular drugs. Furthermore, the KD, which is characterised by the intake of meals rich in fats, has the potential to impact the pharmacokinetics of specific medications with high lipophilicity, hence enhancing their absorption and bioavailability. However, the pharmacodynamic aspects of the KD, in conjunction with various pharmaceutical interventions, can provide either advantageous or detrimental synergistic outcomes. Therefore, it is important to consider the pharmacokinetic and pharmacodynamic interactions that may arise between the KD and various drugs. This assessment is essential not only for ensuring patients' compliance with treatment but also for optimising the overall therapeutic outcome, particularly by mitigating adverse reactions. This highlights the significance and necessity of tailoring pharmacological and dietetic therapies in order to enhance the effectiveness and safety of this comprehensive approach to managing chronic diseases.

##Authors:

• Marinescu SCN
• Apetroaei MM
• Nedea MII
• Arsene AL
• Velescu BȘ
• Hîncu S
• Stancu E
• Pop AL
• Drăgănescu D
• Udeanu DI

------------------------------------------ Info ------------------------------------------

Open Access: True

Additional links:

• https://www.mdpi.com/2072-6643/16/8/1213/pdf?version=1713515448
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11054576

------------------------------------------ Open Access ------------------------------------------

If the paper is behind paywall, please consider uploading it to our google drive anonymously.

You'll have to log on to Google but none of your personal data is stored. I will manually add a link to the file in this post when received.

Upload PDF