Ketogenic Diet: A Balanced Look?

 Ketogenic Diet: A Balanced Look?

WHY YOU SHOULD DO KETO

1. Keto Diets Are Highly Anti-Inflammatory and May Inhibit Cancer Growth

One of the most intriguing benefits of following a well-formulated ketogenic diet is its anti-inflammatory potential and possible anti-cancer effects. Chronic inflammation is linked to a wide range of diseases, including cancer, heart disease, and autoimmune conditions. 

Emerging research suggests ketogenic diets may dampen inflammation through several mechanisms:

• Beta-hydroxybutyrate (BHB), one of the main ketone bodies produced during ketosis, blocks inflammatory pathways associated with disease states. Studies indicate BHB acts as a signaling molecule with epigenetic influence, inhibiting inflammatory genes and cytokines.

• Ketogenic diets have been shown to reduce reactive oxygen species that propagate free radical damage and inflammation. Lower blood sugar levels attained by carb restriction contribute to these antioxidant effects.

• The ketone body acetate is used preferentially by immune cells and plays important signaling roles related to inflammation control. More acetate availability from ketone production may support healthier inflammatory response.

Regarding cancer, ketosis shows potential for slowing tumor growth by providing alternative metabolic fuel while reducing blood glucose levels tumors rely upon. The anti-inflammatory influence of ketosis likely also plays a role in constraining cancer progression. Though research is still early-stage, findings suggest ketogenic diets and fasting may be a promising adjunct therapy for certain cancers while enhancing standard treatments.

2. Appetite Regulation Benefits

Ketosis is also associated with reduced appetite control and food cravings. In fact, many people report decreased hunger while in ketosis despite cutting calories significantly. Several mechanisms explain why ketosis curbs appetite:

• Ketones help directly reduce hunger hormones like ghrelin. Without unbalanced ghrelin signaling, the drive to eat frequently diminishes.

• Elevated levels of ketones promote greater satiety signals through cholecystokinin and other appetite-regulating hormones.

• Without frequent blood sugar swings from carb intake, neurological stimulation to eat is lowered.

• Ketones themselves seem to have a direct appetite-suppressant effect in the brain.

Given how ketosis regulates appetite positively, it becomes easier to maintain the calorie deficit needed for shedding unwanted fat. This contrasts with typical low-fat weight loss diets, which often increase hunger and cravings.

3. Keto Improves Insulin Sensitivity Score (HOMA-IR) and Metabolic Health Markers  

One of the most well-established and significant benefits of carb-restricted ketogenic diets is radically lowered fasting insulin and improved sensitivity scores (HOMA-IR). Persistent high insulin levels contribute heavily to metabolic syndrome, heart disease, obesity-related cancers, and more.

By severely limiting carbohydrate intake, blood sugar and insulin levels are lowered substantially while following a well-formulated ketogenic diet. This effect alone may help mitigate dozens of chronic diseases characterized by underlying insulin resistance.

In fact, human studies lasting from several months up to two years in duration demonstrate the potent effect keto diets have for improving key health markers. These include:

• Lower HbA1c, fasting glucose, and fasting insulin levels

• Reduced triglycerides and increased HDL cholesterol 

• Lowered blood pressure

• Sustained weight and body fat loss

• Reduced abdominal obesity

For those with clear insulin resistance, pre-diabetes, obesity, or metabolic syndrome, adopting a ketogenic diet under medical supervision may be a very impactful lifestyle change, possibly reversing disease progression and help avoid future complications.

4. Ketosis May Extend Lifespan Via Anti-Aging Effects 

An intriguing observation about entering nutritional ketosis is its potential anti-aging effects, observed primarily in animal studies. Although not conclusively proven in humans, early findings suggest ketosis may confer life-extending benefits.

For example, studies show that a ketogenic diet extended mice lifespan by 13%. Researchers proposed several explanations:

• Decreased oxidative damage and inflammation

• Enhanced mitochondrial health and energy production efficiency  

• Increased adaptive stress resilience

• Altered metabolism supporting longevity pathways

If a ketogenic diet extends human lifespan similarly to mice, we may gain anywhere from several extra years to a decade of extra vitality.

WHY YOU SHOULD NOT DO KETO

1. Ketogenic Diets May Negatively Impact LDL Cholesterol

Despite its metabolic benefits, adopting a ketogenic diet does come with potential drawbacks to consider. One commonly cited adverse effect is increased LDL cholesterol, occurring in a subset of individuals following a keto diet. While HDL, triglycerides, and other markers generally improve on keto, elevated total and LDL cholesterol pose safety issues for some people regarding heart disease progression.

Research shows LDL particle size enlargement on keto, shifting particles from small dense type to large buoyant type, which mainstream science associates with lower cardiovascular risk. But some skepticism of this concept exists, necessitating further research. 

Additionally, standard cholesterol panel tests cannot differentiate between LDL particle types. This complicates accuracy in determining individual risk related to physiological changes induced by carbohydrate restriction. Upgraded cholesterol testing (ApoB) provides greater clarity.

Overall, carefully evaluating blood markers is prudent to determine your individual response. 

2. Unclear if Keto Prevents Cardiovascular Disease

Considering the LDL cholesterol concerns covered already, more research would provide greater confidence on long term keto safety for cardiovascular health. Heart disease continues as a leading cause of death, so any diet purported to treat disease warrants rigorous evaluation for prevention.

Some key considerations:

No major clinical trials have tested keto diets against heart disease outcomes yet. However, related markers show promise - improved triglycerides, better HbA1c, lower blood pressure and post-meal glucose spikes all correlate to lower CVD risk.

Anecdotal reports suggest possible cardiovascular benefits for some doing keto, but efficacy is impossible to verify without major controlled trials.

The long term effect of chronic ketosis on vascular function, heart muscle energetics, electrical conductivity, platelet aggregation, and atherosclerotic plaque stability remains largely unexplored territory requiring multi-year trials.

For now, no definitive answer yet exists on whether long term ketogenic dieting prevents cardiovascular events for the average healthy adult or those at elevated risk. But given its metabolic benefits, investigation into these unresolved questions is deserved.

VERDICT

When evaluating the evidence objectively, the data clearly demonstrates low-carbohydrate ketogenic diets provide meaningful benefits for health markers like insulin, body weight, inflammation, blood sugar, and potentially in certain cancers. However, some individuals experience adverse effects like high LDL cholesterol or low thyroid hormone. Ultimately, the most effective nutrition plan is one that you can realistically follow long-term and the one giving you results. 

Several key considerations:

Adhere to an eating pattern you can realistically maintain 

Check biomarkers before and after keto 

Don’t ignore years of nutrition science

• Mediterranean style of eating can still be followed under a keto diet plan. Keto doesn’t have to be carnivore or meat heavy. Find your own balance of plant/animal foods while keeping carbs low. 

Modern medicine isn’t in conflict with Keto

• It’s ok to be be on cholesterol or BP lowering medication while on keto. Ongoing medical oversight ensures safety.

Ketogenic eating may or may not prove the ideal match for you. But choosing real, whole foods that keep insulin and inflammation low provides a solid foundation for supporting long term health. Consistency and biomarkers guide the way.

REFERENCES

Keto & Cancer:

• Ketogenic diet in cancer therapy (2018)

• Effect of Ketogenic Diet on the Clear Cell Renal Cell Carcinoma Cell Growth (link)

• Zhu, H., Bi, D., Zhang, Y., Kong, C., Du, J., Wu, X., Wei, Q., & Qin, H. et al. (2021). "Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations." 

• Römer, M., Dörfler, J., & Huebner, J. (2021). "The use of ketogenic diets in cancer patients: a systematic review."

• Egashira, R., Matsunaga, M., Miyake, A., Hotta, S., Nagai, N., Yamaguchi, C., Takeuchi, M., Moriguchi, M., Tonari, S., Nakano, M., Saito, H., & Hagihara, K. (2023). "Long-Term Effects of a Ketogenic Diet for Cancer."

• Weber et al., 2022, "Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity"​​​​.

• Römer et al., "The use of ketogenic diets in cancer patients: a systematic review"​​.

• Starling, "Ketogenic diet in cancer: insufficient stress response?" This review discusses how ketogenic diets may have an anti-inflammatory effect and could slow tumor growth​​​​.

• Plotti et al., 2020, "Diet and Chemotherapy: The Effects of Fasting and Ketogenic Diet on Cancer Treatment"​​.

Keto & Inflammation:

• DC Shippy  et al, 2020, "β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer's disease pathology in the 5XFAD mouse model."

• YH Youm et al, 2015, The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory diseases.

• Luigi Barrea et al., 2022 "Could very low-calorie ketogenic diets turn off low-grade inflammation in obesity? Emerging evidence."

• Goldberg et al 2020  "Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue."

• Alhamzah et al 2023, Effects of ketogenic diet on oxidative stress and cancer: A literature review

• Greco et al 2016, Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity

• Forsythe et al, 2008 “Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation”

Keto & Appetite:

• A A Gibson et al., 2015, "Do ketogenic diets really suppress appetite? A systematic review and meta-analysis." 

• P Sumithran et al., 2013, "Ketosis and appetite-mediating nutrients and hormones after weight loss." 

• Sarah E Deemer et al., 2020, "Impact of ketosis on appetite regulation-a review.

• Supornpim Chearskul et al., 2008, "Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations." 

• Jessica Roekenes et al., 2021, "Ketogenic diets and appetite regulation." 

Keto & Diet Outcomes and Markers

• Dr. Volek & Dr. Phinney - Translating the Basic Science of Nutritional Ketosis & Keto-Adaptation  (video)

• Steve Phinney - Inflammation, Nutritional Ketosis, and Metabolic Syndrome (video)

• Forsythe et al, 2008 “Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation”

• McKenzie et al, 2017 “A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes”

• Noakes, Manny, et al.  “Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk.” Nutrition & metabolism 3.1 (2006): 7. 

• Volek, Jeff S., et al.  “Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet.” Lipids 44.4 (2009): 297-309. 

• Xiaojie Yuan et al., 2020, "Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis" Nature & Diabetes​​​​​​.

• Samantha L Skow et al., "A Ketogenic Diet is Effective in Improving Insulin Sensitivity in Individuals with Type 2 Diabetes" PubMed​​​​​​.

• Alkhorayef et al, 2023, “Regulatory effects of ketogenic diet on the inflammatory response in obese Saudi women”

Keto & Aging

• Dr. Eric Verdin on Ketogenic Diet Longevity, Beta-Hydroxybutyrate, HDAC Inhibitors & NAD+ (video)

• Dr. John Ramsey - Ketogenic Diets and Aging (video)

• Lian Wang et al., 2021, β-hydroxybutyrate as an Anti-Aging Metabolite

• Megan N Roberts et al., 2017, A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

• Richard L Veech et al., 2017, Ketone bodies mimic the life span extending properties of caloric restriction

• Zsolt Kovács et al., 2021, "Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases"​​.

• Huiyuan Zhu et al., 2022, "Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations"​​.

Keto & Cholesterol (LDL)

• Jesus Salas Noain et al., 2020, "Significant Impact of the Ketogenic Diet on Low-Density Lipoprotein Cholesterol Levels"​​.

• Jonas Burén et al., 2021, "A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial"​​.

• A systematic review and meta-analysis of 38 randomized controlled trials (referenced in Examine.com) examined the association of carbohydrate restriction with LDL particle size and LDL-P in 1,785 healthy adults, finding an increase in LDL peak size and a decrease in LDL-P and small dense LDL concentrations with carbohydrate-restricted diets​​.

• Iulia Iatan, MD, PhD, et al., "Low-Carbohydrate High-Fat 'Keto-Like' Diet Associated With Increased Risk of CVD," which found that a low-carbohydrate high-fat diet was associated with increased levels of LDL-C and apolipoprotein B (apoB) along with a heightened risk of cardiovascular events