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HIGH CARB standard diets vs. HIGH FAT
ketogenic diets and their physiological effects
on the body
Evidence-based review & historical perspective
on the ketogenic diets and ketosis
06.09.2019, Helsinki
Dr. Olli Sovijärvi, M.D.
Free download: biohack.to/keto
1921The birth year of the modern ketogenic diet (Woodyatt, Dr. Wilder).
Woodyatt, R. (1921). Objects and method of diet adjustment in diabetics.
Archives of Internal Medicine 28: 125–141. 

POTENTIAL HEALTH BENEFITS OF KETOSIS
Paoli, A. & Rubini, A. & Volek, J. & Grimaldi, K. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-
carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition 67 (8): 789–796.

Original ketogenic diet model:
• 10-15 grams CHO
• 1 gram PRO / kg bodyweight
• Rest calories from FAT
• FAT to PRO&CHO ratio = 4:1
Composition of ketogenic diets and variants. KD, ketogenic diet; LGIT, low glycaemic index
treatment; MAD, modified Atkins diets; MCT, medium-chain triglyceride; MKT, modified ketogenic
therapy.
KEEP IT CLEAN
THREE DIFFERENT KETONE BODIES
The ketone bodies produced by the
liver are released into the circulation
and delivered into the mitochondria
of the brain, internal organs and
muscles for use in energy
production (ATP). BHB is restored to
acetyl coenzyme A which is utilized
in the citric acid cycle.
• Capric acid (C10) goes to
the liver for ketone formation
• Caprylic acid (C8), if not
converted to ketones in the
liver, can travel to the brain
(crosses BBB) and is
converted to ketones by
astrocytes
MCT-oil benefits
Glycogen stores serve as a
fuel tank for glucose needed
in the body.
For 70 kg adult:
• Liver stores (100-120 g)
• Muscle stores (about 400 g)
The more muscle mass, the bigger
the muscle glycogen stores.
Ketone bodies increase
mitochondrial metabolism and
decrease glycolysis.
Substrates used for
gluconeogenesis when
glucose intake from food is
scarce:
• Lactic acid
• Glycerol (from triglycerides!)
• Alanine (liver)
• Glutamine (kidneys, small
intestine)
• Acetone (ketone body)
Source: Virta Health
We are all fat burners when
given the chance:
• During sleeping
• During fasting
• During exercise
• During ketogenic diet
Ketosis needs to be activated for a high fat
diet to have beneficial effects in the body.
THREE PHASES OF KETO-
ADAPTATION:
• Short-term adaptation (7–14 d)
• Medium-term adaptation
(14–35 days)
• Long-term adaptation (2–12
months)
Ketosis and ketones increase mitochondrial
biogenesis and mitochondrial volume & mass
(particularly in the brain)
β-hydroxybutyrate (BHB) has several metabolic
functions in the body other than energy production
Endogenous inhibition of histone
deacetylases (HDACs)
Ligand for several cell surface
receptors
Downstream products of BHB (acetyl-
CoA, succinyl-CoA and NAD+) have
signalling activities
All these regulatory functions of BHB
have an effect on cellular function
and gene expression
They have important implications for
the pathogenesis and treatment of
metabolic diseases
A ketogenic diet extends longevity and
healthspan in adult mice
Ketogenic diets extends longevity in
adult male mice by 13.6 %
Motor function, memory and muscle
mass are preserved in aged ketogenic
mice
Protein acetylation is increased in the
liver and skeletal muscle of ketogenic
mice
Mechanisms of action of ketogenic diet in epilepsy
• Ketone bodies possess anticonvulsant
effects
• Ketone metabolism prevents convulsive
promoting effects of glucose in neurons
• Ketone bodies decrease levels of
aspartate and glutamate in neurons
• Ketone bodies increase GABA
• In the gut, ketone bodies increase
Akkermansia and Parabacteroides species
which in turn increase GABA and reduce
inflammation
• BHB reduces oxidative stress in the brain
This reduced
glutamatergic signaling
may reduce brain
excitability and potentially
contribute to the
mechanism of the
ketogenic diet.
Ketone bodies inhibit vesicular glutamate transportation.
Ketone bodies:
• Decrease glutamate
• Increase GABA
This leads to calmer state of mind
and neurological ”balance”.
Low-carb and ketogenic diet is more effective on
weight-loss than other iso-caloric weight-loss diets
Physiological reasons:
• Increased energy expenditure
during weight loss maintenance
• Better insulin sensitivity
• Lower leptin
• Higher ghrelin
High carb diets are highly addictive, cause major blood sugar
& insulin swings and are less satiating than high fat diets
The primary outcome was total energy expenditure, measured with doubly labeled
water, by intention-to-treat analysis.
Per protocol analysis included participants who maintained target weight loss,
potentially providing a more precise effect estimate.
Read reviews of 23 studies comparing low carb vs low fat diets on weight loss:
https://www.healthline.com/nutrition/23-studies-on-low-carb-and-low-fat-diets
An open label, non-randomized,
controlled study with 262 and 87
participants with T2D were enrolled in the
CCI and usual care (UC) groups,
respectively.
MACRONUTRIENTS AND THEIR EFFECT ON INSULIN SECRETION
24/7 BLOOD SUGAR ANALYSIS ON A KETOGENIC DIET
Typical change in blood
sugar regulation when
adapted to ketosis
Triglycerides/HDL-ratio
is the most important lipid
measurement on evaluating the
risk for atherosclerosis, CHD, type 2
diabetes, cardiac mortality and
total mortality.
EXERCISE AND KETOSIS
In conclusion, after a period of 3–4 weeks
with total daily carbohydrates at a level
that induces nutritional ketosis, the human
body adapts to be able to use almost all
fat for its fuel.
Conclusion:
Compared to highly trained ultra-endurance athletes consuming
an HC diet, long-term keto-adaptation results in extraordinarily high
rates of fat oxidation, whereas muscle glycogen utilization and
repletion patterns during and after a 3 hour run are similar.
High-carb diets, overeating and high fructose intake cause NAFLD
High Fructose groups consumed 75g
of fructose per day.
Theoretical estimate of liver triglyceride accumulation
Low carbohydrate ketogenic diets work in both isocaloric and
hypocaloric conditions to treat NAFLD
High carb and high sugar diets increase AGEs
AGEs can be ingested with high
temperature processed foods, but also
endogenously formed as a
consequence of a high dietary sugar
intake. Animal models of high sugar
consumption, in particular fructose,
have reported AGE accumulation in
different tissues in association with
peripheral insulin resistance and lipid
metabolism alterations.
Cancer cells thrive on glucose.
Ketogenic diets may help in treating cancer as an adjuvant
therapy, but more evidence is needed.
Preclinical evidence indicating the effect of a KD on tumor growth and progression. The bar chart
shows the number of preclinical studies, which investigated the effect of a KD on different types of
cancer. Colors of the bars represent the result of each study as indicated in the color key.
KETOSIS, FASTING and MOVEMENT have been evolutionary staples in the
history of Homo Sapiens, until recently.
KETOSIS is a natural biological phenomenon which needs to be re-
activated. We can do it.
Thank you :)

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High carb vs. high fat diets and their physiological effects on the body evidence based review & historical perspectives on the ketogenic diets and ketosis

  • 1. HIGH CARB standard diets vs. HIGH FAT ketogenic diets and their physiological effects on the body Evidence-based review & historical perspective on the ketogenic diets and ketosis 06.09.2019, Helsinki Dr. Olli Sovijärvi, M.D.
  • 3.
  • 4.
  • 5. 1921The birth year of the modern ketogenic diet (Woodyatt, Dr. Wilder). Woodyatt, R. (1921). Objects and method of diet adjustment in diabetics. Archives of Internal Medicine 28: 125–141. 

  • 7. Paoli, A. & Rubini, A. & Volek, J. & Grimaldi, K. (2013). Beyond weight loss: a review of the therapeutic uses of very-low- carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition 67 (8): 789–796.

  • 8. Original ketogenic diet model: • 10-15 grams CHO • 1 gram PRO / kg bodyweight • Rest calories from FAT • FAT to PRO&CHO ratio = 4:1
  • 9. Composition of ketogenic diets and variants. KD, ketogenic diet; LGIT, low glycaemic index treatment; MAD, modified Atkins diets; MCT, medium-chain triglyceride; MKT, modified ketogenic therapy.
  • 11.
  • 12.
  • 13. THREE DIFFERENT KETONE BODIES The ketone bodies produced by the liver are released into the circulation and delivered into the mitochondria of the brain, internal organs and muscles for use in energy production (ATP). BHB is restored to acetyl coenzyme A which is utilized in the citric acid cycle.
  • 14. • Capric acid (C10) goes to the liver for ketone formation • Caprylic acid (C8), if not converted to ketones in the liver, can travel to the brain (crosses BBB) and is converted to ketones by astrocytes MCT-oil benefits
  • 15. Glycogen stores serve as a fuel tank for glucose needed in the body. For 70 kg adult: • Liver stores (100-120 g) • Muscle stores (about 400 g) The more muscle mass, the bigger the muscle glycogen stores. Ketone bodies increase mitochondrial metabolism and decrease glycolysis.
  • 16. Substrates used for gluconeogenesis when glucose intake from food is scarce: • Lactic acid • Glycerol (from triglycerides!) • Alanine (liver) • Glutamine (kidneys, small intestine) • Acetone (ketone body)
  • 18.
  • 19. We are all fat burners when given the chance: • During sleeping • During fasting • During exercise • During ketogenic diet
  • 20. Ketosis needs to be activated for a high fat diet to have beneficial effects in the body.
  • 21.
  • 22. THREE PHASES OF KETO- ADAPTATION: • Short-term adaptation (7–14 d) • Medium-term adaptation (14–35 days) • Long-term adaptation (2–12 months)
  • 23. Ketosis and ketones increase mitochondrial biogenesis and mitochondrial volume & mass (particularly in the brain)
  • 24. β-hydroxybutyrate (BHB) has several metabolic functions in the body other than energy production Endogenous inhibition of histone deacetylases (HDACs) Ligand for several cell surface receptors Downstream products of BHB (acetyl- CoA, succinyl-CoA and NAD+) have signalling activities All these regulatory functions of BHB have an effect on cellular function and gene expression They have important implications for the pathogenesis and treatment of metabolic diseases
  • 25. A ketogenic diet extends longevity and healthspan in adult mice Ketogenic diets extends longevity in adult male mice by 13.6 % Motor function, memory and muscle mass are preserved in aged ketogenic mice Protein acetylation is increased in the liver and skeletal muscle of ketogenic mice
  • 26. Mechanisms of action of ketogenic diet in epilepsy • Ketone bodies possess anticonvulsant effects • Ketone metabolism prevents convulsive promoting effects of glucose in neurons • Ketone bodies decrease levels of aspartate and glutamate in neurons • Ketone bodies increase GABA • In the gut, ketone bodies increase Akkermansia and Parabacteroides species which in turn increase GABA and reduce inflammation • BHB reduces oxidative stress in the brain
  • 27. This reduced glutamatergic signaling may reduce brain excitability and potentially contribute to the mechanism of the ketogenic diet. Ketone bodies inhibit vesicular glutamate transportation.
  • 28. Ketone bodies: • Decrease glutamate • Increase GABA This leads to calmer state of mind and neurological ”balance”.
  • 29. Low-carb and ketogenic diet is more effective on weight-loss than other iso-caloric weight-loss diets Physiological reasons: • Increased energy expenditure during weight loss maintenance • Better insulin sensitivity • Lower leptin • Higher ghrelin
  • 30. High carb diets are highly addictive, cause major blood sugar & insulin swings and are less satiating than high fat diets
  • 31. The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate.
  • 32. Read reviews of 23 studies comparing low carb vs low fat diets on weight loss: https://www.healthline.com/nutrition/23-studies-on-low-carb-and-low-fat-diets
  • 33. An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively.
  • 34.
  • 37.
  • 38. Typical change in blood sugar regulation when adapted to ketosis
  • 39. Triglycerides/HDL-ratio is the most important lipid measurement on evaluating the risk for atherosclerosis, CHD, type 2 diabetes, cardiac mortality and total mortality.
  • 41.
  • 42. In conclusion, after a period of 3–4 weeks with total daily carbohydrates at a level that induces nutritional ketosis, the human body adapts to be able to use almost all fat for its fuel.
  • 43. Conclusion: Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.
  • 44. High-carb diets, overeating and high fructose intake cause NAFLD
  • 45.
  • 46. High Fructose groups consumed 75g of fructose per day. Theoretical estimate of liver triglyceride accumulation
  • 47. Low carbohydrate ketogenic diets work in both isocaloric and hypocaloric conditions to treat NAFLD
  • 48. High carb and high sugar diets increase AGEs AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations.
  • 49. Cancer cells thrive on glucose. Ketogenic diets may help in treating cancer as an adjuvant therapy, but more evidence is needed. Preclinical evidence indicating the effect of a KD on tumor growth and progression. The bar chart shows the number of preclinical studies, which investigated the effect of a KD on different types of cancer. Colors of the bars represent the result of each study as indicated in the color key.
  • 50. KETOSIS, FASTING and MOVEMENT have been evolutionary staples in the history of Homo Sapiens, until recently. KETOSIS is a natural biological phenomenon which needs to be re- activated. We can do it. Thank you :)