Ketogenic Diet
Note: References for this page will be marked as [KD Ref. ?] meaning Ketogenic Diet Reference ? (number).
Otherwise references will be listed as on the other pages - [Ref.1.23] for example.
Recommended books: Nourishing Traditions (by Sally Fallon)
The Art and Science of Low Carbohydrate Living (Stephen Phinney, Jeff Volek)
The New Atkins for a New You (Dr. Eric C. Westman, Dr. Stephen D. Phinney, Jeff S. Volek)
Videos: Optimising Weight and Health with an LCHF Diet, part 2, part 3 (Stephen Phinney)
The Many Facets of Keto-Adaptation (Jeff Volek)
Prof. Tim Noakes - 'Medical aspects of the low carbohydrate lifestyle'
Articles: The Inuit Paradox
Description
Carbohydrates: 55[g] maximum; multiply by 4 to get calories from carbohydrates
Proteins: about 1.0 .. 2.0[g/kg]; multiply by 4 to get calories from proteins
Fats: the remaining calories /9 to get in [g]; multiply [g] by 9 to get calories from fats
ideal omega 6 : omega 3 ratio is 1:1
Notes:
Consider buying ketosis/ketones test strips to monitor if ketosis is achieved.
Recommended equipment (by Jeff Volek [23:30]) (link, link2).
Processed food is not allowed.
"Home made", "wild/organic/grass fed", "raw/fermented", "whole/full fat" are preferred.
Implementing ketogenic diet as a reduced calorie diet will be more beneficial for cancer.
The diet needs to be maintained for at least 5 months after the cancer can no longer be detected (mentioned
in 1 video).
Reduced calorie diet is usually 10..20% calorie reduction by diet and the same amount (10..20%) calorie reduction
by exercises. For cancer some sources mention calories around 1200 .. 1500 (i.e. about 60 .. 75% of regular
level). Such low calorie intake is actually normal at the beginning of the ketogenic diet, while the body burns the
stored fat. Ratio "fat" : "carbs + proteins" was 4:1 (by weight => ~150[g] fat : 40..50[g] proteins) for anti cancer diet.
Proteins are reduced because cancer can utilize glutamine. In addition drugs were used to block various cancer
metabolic paths ...
This would be very difficult anti-cancer protocol and will need medical supervision.
Should be combined with HBOT:
https://www.youtube.com/watch?v=3fM9o72ykww
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673985/
ketogenic diet (no calorie restriction - but it may be self restricting calorie intake) + HBOT led to 2x longer life.
For an anti cancer keto diet one should include fats, and spices with proven anti cancer properties:
- olive oil, flax seed oil, coconut oil, cocoa, cinnamon ...
Ketogenic diet is beneficial for cancer patients with cachexia (KD Ref.4)
Absolute minimum calorie intake per day are (link):
for men: (9.99 x weight) + (6.25 x height) – (4.92 x age) + 5
for women: (9.99 x weight) + (6.25 x height) – (4.92 x age) – 161
where: weight is in [kg], height is in [cm] and age is in [years]
Example Food List:
Fats:
Avocado, (from grass fed beef) Butter, Ghee, Coconut oil, Olive oil, flax seed oil, high omega 3 fish/krill oil
almond butter, cocoa butter
Meats:
(wild; salmon, cod, sardines, herring) fish;
avoid fish with potentially high mercury content (tuna, marlin, shark) (link)
sea fish is preferred over fresh water fish.
avoid farmed fish
fermented fish is preferred;
row fish is not recommended due to possible worm parasites. Fish frozen for more than 7 days is OK. (link)
shellfish, clams, oysters, shrimp, lobster, crab
eggs
(organic, grass fed) Beef, Veal, Goat, Lamb, Pork (other wild game)
(organic) poultry, turkey
(organic) organ meats - liver, hearts, kidney - all organ meats are preferred over regular meat
Vegetables, fruits and berries:
avocado
mushrooms
kale, chard, onion, garlic, parsley, spinach, arugula, turnips, celery, (any) sprouts
broccoli, cauliflower, cabbage, brussels sprouts,
lentils, green beans
(cooked) tomato (paste),
carrots
(hot) pepper, cucumber
lemon, lime
home made fermented vegetables, berries and fruit without added sugar:
pickles, pepper, onion, (wild) blueberries, strawberries, raspberries, grapes, fruits (link), sauerkraut
Dairy:
heavy whipping cream
(goat, sheep) cheese (preferably old, from raw milk), feta cheese, cream cheese, cottage cheese, sour cream
(home made) kefir, yogurt
Nuts and seeds:
(raw) coconut
(raw) almonds, walnuts, pistachios, macadamia, brazil nuts
chia,
(raw) flax seeds, hemp seeds, pumpkin seeds, sesame seeds
Beverages:
water, green/black/herbal tea, coffee
Sweeteners:
stevia
Spices:
(celtic) sea salt, himalayan salt,
cinnamon
black pepper,
turmeric
basil, cayenne pepper, chili powder, cumin, oregano, rosemary, sage, ...
Fiber (add from supplements as needed):
min daily requirements: ~25[g] for women, ~38[g] for men (link)
Supplements (estimated requirements):
Fiber: ~10[g]
Magnesium: 100[mg]
Potassium: 1000[mg]
Vit. E (optional): - 100[IU]
Vit. D: 4,000 [IU]
Other resources:
http://naturalsolutions.nz/ketogenic
Controlling your cravings (link):
Cravings What You Need What to Eat
Chocolate Magnesium Nuts, seeds
Sugary Foods Chromium Broccoli, Cheese
Carbon Spinach
Phosphorus Chicken, beef, eggs
Sulphur Cauliflower, broccoli
Tryophan Cheese, lamb, liver
Bread, Pasta, Carbs Nitrogen High protein meat
Oil/Fatty Foods Calcium Cheese, Broccoli, Spinach
Salty Foods Chloride Fish
Silicon Nuts, seeds
Otherwise references will be listed as on the other pages - [Ref.1.23] for example.
Recommended books: Nourishing Traditions (by Sally Fallon)
The Art and Science of Low Carbohydrate Living (Stephen Phinney, Jeff Volek)
The New Atkins for a New You (Dr. Eric C. Westman, Dr. Stephen D. Phinney, Jeff S. Volek)
Videos: Optimising Weight and Health with an LCHF Diet, part 2, part 3 (Stephen Phinney)
The Many Facets of Keto-Adaptation (Jeff Volek)
Prof. Tim Noakes - 'Medical aspects of the low carbohydrate lifestyle'
Articles: The Inuit Paradox
Description
Carbohydrates: 55[g] maximum; multiply by 4 to get calories from carbohydrates
Proteins: about 1.0 .. 2.0[g/kg]; multiply by 4 to get calories from proteins
Fats: the remaining calories /9 to get in [g]; multiply [g] by 9 to get calories from fats
ideal omega 6 : omega 3 ratio is 1:1
Notes:
Consider buying ketosis/ketones test strips to monitor if ketosis is achieved.
Recommended equipment (by Jeff Volek [23:30]) (link, link2).
Processed food is not allowed.
"Home made", "wild/organic/grass fed", "raw/fermented", "whole/full fat" are preferred.
Implementing ketogenic diet as a reduced calorie diet will be more beneficial for cancer.
The diet needs to be maintained for at least 5 months after the cancer can no longer be detected (mentioned
in 1 video).
Reduced calorie diet is usually 10..20% calorie reduction by diet and the same amount (10..20%) calorie reduction
by exercises. For cancer some sources mention calories around 1200 .. 1500 (i.e. about 60 .. 75% of regular
level). Such low calorie intake is actually normal at the beginning of the ketogenic diet, while the body burns the
stored fat. Ratio "fat" : "carbs + proteins" was 4:1 (by weight => ~150[g] fat : 40..50[g] proteins) for anti cancer diet.
Proteins are reduced because cancer can utilize glutamine. In addition drugs were used to block various cancer
metabolic paths ...
This would be very difficult anti-cancer protocol and will need medical supervision.
Should be combined with HBOT:
https://www.youtube.com/watch?v=3fM9o72ykww
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673985/
ketogenic diet (no calorie restriction - but it may be self restricting calorie intake) + HBOT led to 2x longer life.
For an anti cancer keto diet one should include fats, and spices with proven anti cancer properties:
- olive oil, flax seed oil, coconut oil, cocoa, cinnamon ...
Ketogenic diet is beneficial for cancer patients with cachexia (KD Ref.4)
Absolute minimum calorie intake per day are (link):
for men: (9.99 x weight) + (6.25 x height) – (4.92 x age) + 5
for women: (9.99 x weight) + (6.25 x height) – (4.92 x age) – 161
where: weight is in [kg], height is in [cm] and age is in [years]
Example Food List:
Fats:
Avocado, (from grass fed beef) Butter, Ghee, Coconut oil, Olive oil, flax seed oil, high omega 3 fish/krill oil
almond butter, cocoa butter
Meats:
(wild; salmon, cod, sardines, herring) fish;
avoid fish with potentially high mercury content (tuna, marlin, shark) (link)
sea fish is preferred over fresh water fish.
avoid farmed fish
fermented fish is preferred;
row fish is not recommended due to possible worm parasites. Fish frozen for more than 7 days is OK. (link)
shellfish, clams, oysters, shrimp, lobster, crab
eggs
(organic, grass fed) Beef, Veal, Goat, Lamb, Pork (other wild game)
(organic) poultry, turkey
(organic) organ meats - liver, hearts, kidney - all organ meats are preferred over regular meat
Vegetables, fruits and berries:
avocado
mushrooms
kale, chard, onion, garlic, parsley, spinach, arugula, turnips, celery, (any) sprouts
broccoli, cauliflower, cabbage, brussels sprouts,
lentils, green beans
(cooked) tomato (paste),
carrots
(hot) pepper, cucumber
lemon, lime
home made fermented vegetables, berries and fruit without added sugar:
pickles, pepper, onion, (wild) blueberries, strawberries, raspberries, grapes, fruits (link), sauerkraut
Dairy:
heavy whipping cream
(goat, sheep) cheese (preferably old, from raw milk), feta cheese, cream cheese, cottage cheese, sour cream
(home made) kefir, yogurt
Nuts and seeds:
(raw) coconut
(raw) almonds, walnuts, pistachios, macadamia, brazil nuts
chia,
(raw) flax seeds, hemp seeds, pumpkin seeds, sesame seeds
Beverages:
water, green/black/herbal tea, coffee
Sweeteners:
stevia
Spices:
(celtic) sea salt, himalayan salt,
cinnamon
black pepper,
turmeric
basil, cayenne pepper, chili powder, cumin, oregano, rosemary, sage, ...
Fiber (add from supplements as needed):
min daily requirements: ~25[g] for women, ~38[g] for men (link)
Supplements (estimated requirements):
Fiber: ~10[g]
Magnesium: 100[mg]
Potassium: 1000[mg]
Vit. E (optional): - 100[IU]
Vit. D: 4,000 [IU]
Other resources:
http://naturalsolutions.nz/ketogenic
Controlling your cravings (link):
Cravings What You Need What to Eat
Chocolate Magnesium Nuts, seeds
Sugary Foods Chromium Broccoli, Cheese
Carbon Spinach
Phosphorus Chicken, beef, eggs
Sulphur Cauliflower, broccoli
Tryophan Cheese, lamb, liver
Bread, Pasta, Carbs Nitrogen High protein meat
Oil/Fatty Foods Calcium Cheese, Broccoli, Spinach
Salty Foods Chloride Fish
Silicon Nuts, seeds
Food information:
1. Complete Guide to Fats & Oils on a Low-Carb Ketogenic Diet
Omega 6 : Omega 3
krill oil: 1 : 12
fish oil: 1 : 6
flax seed oil: 1 : 3
Clarified butter (Ghee), butter: 1 : 1
Grass fed beef: 1.5 : 1
coconut oil: 2 : 1
macadamia oil: 2 : 1
hemp seed oil: 2.5 : 1
cocoa butter: 3 : 1
walnut oil: 7 : 1
Bacon: 12 : 1
Duck, Goose, Chicken fat: 12 : 1
avocado, olive oil: 12 : 1
pumpkin seed oil: 20 : 1
almond oil: 28 : 1
peanut oil: 34 : 1
sesame oil: 45 : 1
1. Complete Guide to Fats & Oils on a Low-Carb Ketogenic Diet
Omega 6 : Omega 3
krill oil: 1 : 12
fish oil: 1 : 6
flax seed oil: 1 : 3
Clarified butter (Ghee), butter: 1 : 1
Grass fed beef: 1.5 : 1
coconut oil: 2 : 1
macadamia oil: 2 : 1
hemp seed oil: 2.5 : 1
cocoa butter: 3 : 1
walnut oil: 7 : 1
Bacon: 12 : 1
Duck, Goose, Chicken fat: 12 : 1
avocado, olive oil: 12 : 1
pumpkin seed oil: 20 : 1
almond oil: 28 : 1
peanut oil: 34 : 1
sesame oil: 45 : 1
References
1. Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer.
"After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in
the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism
of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue
after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose
metabolism."
2. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy
"In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels
or improve survival.
... The classic ketogenic diet is a high-fat and low-carbohydrate dietetic approach raising levels of serum ketone
bodies, i.e. acetoacetate, 3-hydroxybutyrate (from less than 0.1 mM to 0.2-1.8 mM and 2-5 mM, respectively) and
acetone, and lowering brain glucose uptake.
... A reduction of tumor growth under conditions of caloric restriction and/or weight loss has repeatedly been shown
in glioma models
... no decline in blood glucose concentrations when a ketogenic diet was administered in unrestricted amounts
... a reduction in circulating IGF-1 levels would have been expected only under conditions of caloric restriction
... However, an unrestricted ketogenic diet was not effective as a monotherapy in the xenograft model applied.
A combination of a ketogenic diet with strategies inhibiting glycolysis or interfering with the tumor's energy supply,
such as vascular disrupting or antiangiogenic agents, might result in synergistic antitumor effects and is worth
further investigation."
3. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
"Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can,
in some cases, completely remove the need for medication. ... Recent work over the last decade or so has provided
evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic
ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease
risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical
methods of treatment, which are often lifelong with significant side effects, calls for serious investigation.very-low-
carbohydrate ketogenic diets (VLCKD) could have a therapeutic role in numerous diseases. The use of VLCKD in
treating epilepsy has been well established for many decades ... clearly, if nutritional intervention can reduce reliance
on pharmaceutical treatments it would bring significant benefits from an economic as well as a social point of view
given the current US $750 billion annual cost of pharmaceuticals. ...
Ketogenic diets are characterized by a reduction in carbohydrates (usually to less than 50 g/day) and a relative
increase in the proportions of protein and fat ...
What is ketosis?
... After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves
become insufficient ... The central nervous system (CNS) cannot use fat as an energy source; hence, it normally utilizes
glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources ...
derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes
and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies
(KBs), that is, acetoacetate, ß-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs
principally in the mitochondrial matrix in the liver.
Blood levels Normal diet Ketogenic diet Diabetic ketoacidosis
Glucose (mg/dl) 80–120 65–80 >300
Insulin (µU/l) 6–23 6.6–9.4 0
KB conc (mx2133/l) 0.1 7/8 >25
pH 7.4 7.4 <7.3
We would like to emphasize that ketosis is a completely physiological mechanism and it was the biochemist Hans Krebs
who first referred to physiological ketosis to differentiate it from the pathological keto acidosis seen in type 1 diabetes.
In physiological ketosis (which occurs during very-low-calorie ketogenic diets), ketonemia reaches maximum levels of
7/8 mmol/l (it does not go higher precisely because the CNS efficiently uses these molecules for energy in place of
glucose) and with no change in pH, whereas in uncontrolled diabetic ketoacidosis it can exceed 20 mmol/l with a
concomitant lowering of blood pH.
Therapeutic roles of ketogenic diets
Strong evidence
Weight loss
1. Reduction in appetite due to higher satiety effect of proteins, effects on appetite control hormones and to a possible
direct appetite-suppressant action of the KBs.
2. Reduction in lipogenesis and increased lipolysis.
3. Reduction in the resting respiratory quotient and, therefore, greater metabolic efficiency in consuming fats.
4. Increased metabolic costs of gluconeogenesis and the thermic effect of proteins.
Cardiovascular disease
Type 2 diabetes (T2D)
... A person with insulin resistance will divert a greater proportion of dietary carbohydrate to the liver where much of it
is converted to fat, as opposed to being oxidized for energy in skeletal muscle. ... this greater conversion of dietary
carbohydrate into fat, much of it entering the circulation as saturated fat, is a metabolic abnormality that significantly
increases risk for diabetes and heart disease. Thus, insulin resistance functionally manifests itself as ‘carbohydrate
intolerance'. When dietary carbohydrate is restricted to a level below which it is not significantly converted to fat (a
threshold that varies from person to person), signs and symptoms of insulin resistance improve or often disappear
completely.
... withdrawal of insulin and major weight loss in a matter of weeks in T2D individuals who were fed a very-low-calorie
and -carbohydrate diet. ... fed obese T2D individuals two types of hypocaloric (650 kcal) diets for 3 weeks, they were
matched for protein but one was much lower in carbohydrate content (24 vs 94 g/day). As expected, the lower-
carbohydrate diet resulted in significantly greater levels of circulating ketones (~3 mmol/l), which was strongly
associated with a lower hepatic glucose output. ... higher levels of ketones are associated with more favourable effects
on glycaemic control in diabetics. ... fed a low-carbohydrate (<20 g/day) diet for 2 weeks. Plasma glucose fell from 7.5
to 6.3 mmol/l, haemoglobin A1c decreased from 7.3 to 6.8% and there were dramatic improvements (75%) in insulin
sensitivity.
T2D individuals were prescribed a well-formulated ketogenic diet for 56 weeks, and significant improvements in both
weight loss and metabolic parameters were seen at 12 weeks and continued throughout the 56 weeks as evidenced by
improvements in fasting circulating levels of glucose (-51%), total cholesterol (-29%), high-density lipoprotein–
cholesterol (63%), low-density lipoprotein–cholesterol (-33%) and triglycerides (-41%). It is of interest to note that in a
recent study in overweight non/diabetic subjects, it was reported that during ketosis fasting glucose was not affected,
but there was an elevation in post-prandial blood glucose concentration. This data suggests a different effect of ketosis
on glucose homeostasis in diabetic and non-diabetic individuals. Other studies support the long-term efficacy of
ketogenic diets in managing complications of T2D. Although significant reductions in fat mass often results when
individuals restrict carbohydrate, the improvements in glycaemic control, haemoglobin A1c and lipid markers, as well
as reduced use or withdrawal of insulin and other medications in many cases, occurs before significant weight loss
occurs. Moreover, in isocaloric experiments individuals with insulin resistance showed dramatically improved markers
of metabolic syndrome than diets lower in fat. It is interesting in this respect that a recent extremely large
epidemiological study reported that diabetes risk is directly correlated, in an apparently causative manner, with sugar
intake alone, independently of weight or sedentary lifestyle. Epilepsy
... 30–40% reduction in seizures compared with comparative controls, and the review authors reported that in children
the effects were ‘comparable to modern antiepileptic drugs'. The main drawback with the ketogenic diet was difficult
tolerability and high dropout rates ...
... The recent research reviewed here demonstrate improvements in many risk factors, such as weight, saturated fats,
inflammation and other biomarkers, as a consequence of consuming well-formulated low-carbohydrate diets ...
Emerging evidence
Acne
Cancer
There is evidence that hyperinsulinaemia, hyperglycaemia and chronic inflammation may affect the neoplastic process
through various pathways, including the insulin/IGF-1 pathway, and most cancer cells express insulin and IGF-1
receptors. Insulin has been shown to stimulate mitogenesis (even in cells lacking IGF-1 receptors)50 and it may also
contribute by stimulating multiple cancer mechanisms, including proliferation, protection from apoptotic stimuli,
invasion and metastasis.
... tumour cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin ...
Polycystic ovary syndrome (PCOS)
... symptoms include hyperandrogenism, ovulatory dysfunction, obesity, insulin resistance and subfertility.
Insulin resistance and related hyperinsulinaemia is actually a very common feature affecting about 65–70% of women
with PCOS;73 it is seen most frequently in obese patients, affecting 70–80%, compared with only 20–25% of lean PCOS
sufferers. ... Women with PCOS frequently demonstrate many of the signs related to metabolic syndrome, such as
insulin resistance, obesity, glucose intolerance, T2D, dyslipidemia and also high levels of inflammation.
... we only have preliminary evidence of the positive effects of VLCKD in PCOS...
Neurological diseases
... epilepsy, including head ache, neurotrauma, Alzheimer's and Parkinson's disease, sleep disorders, brain cancer,
autism and multiple sclerosis. ... act as neuroprotective agents by raising ATP levels and reducing the production of
reactive oxygen species in neurological tissues, together with increased mitochondrial biogenesis, which may help to
enhance the regulation of synaptic function. Moreover, the increased synthesis of polyunsaturated fatty acids
stimulated by a KD may have a role in the regulation of neuronal membrane excitability ... reducing glucose
metabolism, ketogenic diets may activate anticonvulsant mechanisms ... In addition, caloric restriction per se has been
suggested to exert neuroprotective effects, including improved mitochondrial function, decreased oxidative stress and
apoptosis, and inhibition of proinflammatory mediators, such as the cytokines tumour necrosis factor-a and
interleukins.
Alzheimer's disease
... In an animal model of Alzheimer's disease, transgenic mice consuming a ketogenic diet exhibited better
mitochondrial function and less oxidative stress and ß-amyloid deposition when compared with normally fed
controls. ...
Parkinson's disease
... typical mitochondrial respiratory chain damage that occurs in animal models of Parkinson's disease was reduced by
a ketogenic diet ...
Brain trauma
... ketogenic diet reduced post-traumatic cognitive and motor function impairment, at least in a rat model ...
Amyotrophic lateral sclerosis
The effect of a ketogenic diet on respiratory function
Potential risks of ketogenic diets
If we equate de facto ketogenic diets with high-protein diets (which is not always correct) then the risks proposed by
critics of this type of dietary approach are essentially those of possible kidney damage due to high levels of nitrogen
excretion during protein metabolism, which can cause an increase in glomerular pressure and hyperfiltration ... it
should be noted that ketogenic diets are only relatively high in protein18, 106 and that some recent studies have
demonstrated that VLCKD can even cause a regression of diabetic nephropathy in mice. With regard to possible
acidosis during VLCKD, as the concentration of KBs never rises above 8 mmol/l10 this risk is virtually inexistent in
subjects with normal insulin function.
... Further studies are warranted to investigate more in detail the potential therapeutic mechanisms, its effectiveness
and safety"
4. The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer
"KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7%
in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the
KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean
survival time compared to controls.
... While many primary tumors can be controlled with conventional therapies like surgery, chemotherapy, and
radiation, these treatments are often ineffective against metastatic disease and in some cases may promote cancer
progression and metastasis ...
Abnormal energy metabolism is a consistent feature of most tumor cells across all tissue types. In the 1930 s, Otto
Warburg observed that all cancers expressed high rates of fermentation in the presence of oxygen. This feature,
known as The Warburg Effect, is linked to mitochondrial dysfunction and genetic mutations within the cancer cell.
These defects cause cancers to rely heavily on glucose for energy, a quality that underlies the use of
fluorodeoxyglucose-PET scans as an important diagnostic tool for oncologists. Ketogenic diets are high fat, low
carbohydrate diets that have been used for decades to treat patients with refractory epilepsy. Ketogenic diets also
suppress appetite naturally thus producing some body weight loss. Dietary energy reduction (DER) lowers blood
glucose levels, limiting the energy supply to cancer cells, while elevating circulating blood ketone levels. Ketone
bodies can serve as an alternative energy source for those cells with normal mitochondrial function, but not for
cancer cells. DER has been shown to have anti-tumor effects in a variety of cancers, including brain, prostate,
mammary, pancreas, lung, gastric, and colon. DER produces anti-cancer effects through several metabolic pathways,
including inhibition of the IGF-1/PI3K/Akt/HIF-1a pathway which is used by cancer cells to promote proliferation
and angiogenesis and inhibit apoptosis. Additionally, DER induces apoptosis in astrocytoma cells, while protecting
normal brain cells from death through activation of adenosine monophosphate kinase (AMPK).
Tumors possess abnormal vasculature which blocks adequate tissue perfusion, leading to the presence of hypoxic
regions that promote chemotherapy and radiation resistance. In fact, hypoxic cancer cells are three-times more
resistant to radiation therapy than are well-oxygenated cells [48]. In addition to decreasing the efficacy of standard
care, tumor hypoxia activates a number of oncogene pathways, largely through the HIF-1 transcription factor, which
promote tumor growth, metastasis, angiogenesis, and inhibit apoptosis.
Hyperbaric oxygen therapy (HBO2T) involves administration of 100% oxygen at elevated pressure (greater than sea
level, or 1 ATA). HBO2T increases plasma oxygen saturation which facilitates oxygen delivery to the tissue
independent of hemoglobin O2 saturation. The potential benefit of using HBO2T to combat the cancer-promoting
effects of tumor hypoxia is clear. HBO2T alone has been shown to inhibit tumor growth, reduce tumor blood vessel
density, and induce the preferential expression of anti-cancer genes in rat models of mammary tumors. Additionally,
radiation and many chemotherapy drugs work by producing free radicals within the tumors, leading to cell death.
HBO2T enhances tumor-cell production of reactive oxygen species which contributes to the synergistic effects of
HBO2T as an adjuvant treatment to standard care. Indeed, HBO2T enhances the efficacy of both radiation and
chemotherapy in animal models.
... We found that the KD fed ad libitum significantly increased mean survival time in mice with metastatic cancer ... It
is important to note that KD-fed animals lost approximately 10% of their body weight over the course of the study ...
possibility that mice found the KD to be less palatable and were self-restricting caloric intake. As calorie restriction is
known to elicit profound anti-cancer effects, the ketogenic diet may inhibit cancer progression in part by indirect
dietary energy restriction ... suggesting that ketone elevation itself also contributes to the anti-cancer efficacy of the
KD ... Combining these therapies (KD with HBO2T) nearly doubled survival time in mice with metastatic cancer ...
By day 7, all animals on a ketogenic diet had significantly lower blood glucose levels than controls. As it has been
shown that tumor growth is directly correlated to blood glucose levels, this decrease in blood glucose concentration
likely contributed to the trend of decreased tumor bioluminescence and rate of tumor growth seen in KD-fed animals.
Nebeling et al. demonstrated that the KD significantly decreased glucose uptake in pediatric brain tumor patients by
FDG-PET analysis. This clinical data suggests decreased glucose delivery to the tumor is a causal mechanism in KD
treatment. All KD-fed mice showed a trend of elevated blood ketones throughout the study; however, only
KD+HBO2T mice had significantly higher ketones than controls on day 7. As ketones are metabolized exclusively
within the mitochondria, cancer cells with damaged mitochondria are unable to adequately use them for energy. ...
ketone bodies have anti-cancer effects themselves, possibly through inhibition of glycolytic enzymes ...
Potential concern may arise regarding the use of a diet therapy for cancer patients susceptible to cachexia. While low
carbohydrate or ketogenic diets promote weight loss in overweight individuals, they are also known to spare muscle
wasting during conditions of energy restriction and starvation. In an animal model of cancer cachexia, administration
of a low carbohydrate, high fat diet prevented weight loss of the animals while simultaneously decreasing tumor size.
Similar effects were described in human cancer patients ... Furthermore, when given as an adjuvant treatment to
advanced cancer patients, the KD improves quality of life and enhances the efficacy of chemotherapy treatment in
the clinic ...
It is important to look for synergistic interactions between therapies which may increase the efficacy of cancer
treatment. Scheck and coworkers reported complete remission without recurrence in 9 of 11 mice with glioma by
combining the KD with radiation. Marsh, et al. reported synergy between the restricted ketogenic diet and the
glycolysis inhibitor 2-deoxyglucose. Might adding HBO2T to these combination therapies elicit even better results?
Similarly, might the use of adjuvant therapies like KD and HBO2T enhance patient response to standard care?"
5. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.
"The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549
xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined
with carboplatin and radiation, relative to control. ... These results show that a ketogenic diet enhances radio-
chemo-therapy responses in lung cancer xenografts ..."
6. How Does the Ketogenic Diet Work? Four Potential Mechanisms
"Dietary therapies that alter the body’s energy source are effective in treating epilepsy and show promise in treating
other neurological and non-neurological conditions. These therapies include the classical ketogenic diet, a high fat,
low carbohydrate, adequate protein diet, and its variants such as the medium chain triglyceride diet, modified Atkins
diet, and low glycemic index treatment. ...
Animal and clinical studies suggest that the ketogenic diet may be useful in treating neurodegenerative diseases such
as Alzheimer, Parkinson, and amyotrophic lateral sclerosis. The diet may also limit neuronal dysfunction from
traumatic brain injury and stroke. Non-neurological conditions in which the diet may have a therapeutic role include
cancer and diabetic nephropathy. ...
... Since the ketogenic diet has anti-seizure effects, the consumption of a high fat, low carbohydrate diet ketogenic diet
must somehow alter neuronal excitability. The underlying molecular mechanisms are not fully understood ... The
proposed mechanisms reviewed here involve carbohydrate reduction, adenosine triphosphate (ATP)-sensitive
potassium channels and mitochondrial metabolism, the mammalian target of rapamycin pathway, and glutamatergic
synaptic transmission.
Carbohydrate Reduction
... All versions of the ketogenic diet including variants such as the modified Atkins diet, low glycemic index treatment,
and fasting/calorie restriction limit carbohydrates. Indeed, seizures recur within one hour of an intravenous infusion
of glucose in children with well-controlled seizures on a medium chain triglyceride diet ... The glucose analog
2-deoxy-D-glucose partially inhibits glycolysis and exerts a novel anti-seizure profile in animal models. 2-deoxy-D-
glucose is generally safe and well tolerated clinically as a tracer in positron emission studies and adjunctive therapy in
cancer trials. ...
... these results suggest that 2-deoxy-D-glucose has a unique anticonvulsant and antiepileptogenic profile, unlike that
of any currently available drug. ... However, the clinical use of 2-deoxy-D-glucose will require additional safety data
because of the association between orally administered 2-deoxy-D-glucose and cardiotoxicity in some models
Activation of ATP-sensitive potassium channels by mitochondrial metabolism
Inhibition of the mammalian target of rapamycin pathway
... This pathway responds indirectly to a variety of metabolic inputs including the insulin receptor, fasting,
ATP/adenosine monophosphate (AMP) ratio, and hypoglycemia. ... However, excessive activity of this pathway is
pathological and leads to human disorders including tuberous sclerosis complex, Cowden syndrome, and some forms of
cancer. ...
Inhibition of glutamatergic synaptic transmission
... One clinical study showed better seizure control with higher serum ß-hydroxybutyrate levels, but most other clinical
reports found no or only a transient correlation between serum ß-hydroxybutyrate or acetoacetate concentrations and
seizure control. ... Acetone has anti-seizure properties in several animal models... Accordingly, acetoacetate and ß-
hydroxybutyrate inhibit vesicular glutamate transporters ... Of the two ketones, acetoacetate is more potent, with a
half maximal inhibitory concentration less than 1 mM in physiological chloride concentrations, compared to 1–10 mM
for ß-hydroxybutyrate. ..."
7. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports.
"Two female pediatric patients with advanced stage malignant Astrocytoma tumors.
Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones
were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at
the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill
development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of
disease progression."
8. Post on a news group:
"Gloria says:
You should watch the program”Know the Cause” and follow some of the information. My husband had bladder cancer
and my son had kidney and anal cancer. I put them on the Phase l diet, gave them anti-fungals (caprylic acid, olive leaf
extract and oil of oregano w/P73). You rotate these every 3 weeks using 1 at a time. I put them on extra strength
NSC-24 beta glucan and Dr. Oh’hiras probiotics. Radiation and chemo kills you immune system, beta glucan and
probiotics put them back. You will have more energy and will not get sick. Both my husband and son are now cancer
free. You can read Doug Kaufman’s books or listen to his program to be educated."
Note: Phase 1 diet is actually not ketogenic but it is worth considering combination of some of the antifungal supplements and diet guidelines.
9. Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest.
Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.
10. Studies on ketosis
11. Utililizing a ketogenic diet to target cachexia syndrome in pancreatic cancer
12. Neuroprotective and disease-modifying effects of the ketogenic diet
13. Methylglyoxal and the Ketogenic Diet – The Miraculous Compound that got Bad-Mouthed by Ignorance
14. KETONE BODY THERAPY: From the Ketogenic Diet to the Oral Administration of Ketone Ester
1. Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer.
"After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in
the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism
of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue
after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose
metabolism."
2. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy
"In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels
or improve survival.
... The classic ketogenic diet is a high-fat and low-carbohydrate dietetic approach raising levels of serum ketone
bodies, i.e. acetoacetate, 3-hydroxybutyrate (from less than 0.1 mM to 0.2-1.8 mM and 2-5 mM, respectively) and
acetone, and lowering brain glucose uptake.
... A reduction of tumor growth under conditions of caloric restriction and/or weight loss has repeatedly been shown
in glioma models
... no decline in blood glucose concentrations when a ketogenic diet was administered in unrestricted amounts
... a reduction in circulating IGF-1 levels would have been expected only under conditions of caloric restriction
... However, an unrestricted ketogenic diet was not effective as a monotherapy in the xenograft model applied.
A combination of a ketogenic diet with strategies inhibiting glycolysis or interfering with the tumor's energy supply,
such as vascular disrupting or antiangiogenic agents, might result in synergistic antitumor effects and is worth
further investigation."
3. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
"Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can,
in some cases, completely remove the need for medication. ... Recent work over the last decade or so has provided
evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic
ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease
risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical
methods of treatment, which are often lifelong with significant side effects, calls for serious investigation.very-low-
carbohydrate ketogenic diets (VLCKD) could have a therapeutic role in numerous diseases. The use of VLCKD in
treating epilepsy has been well established for many decades ... clearly, if nutritional intervention can reduce reliance
on pharmaceutical treatments it would bring significant benefits from an economic as well as a social point of view
given the current US $750 billion annual cost of pharmaceuticals. ...
Ketogenic diets are characterized by a reduction in carbohydrates (usually to less than 50 g/day) and a relative
increase in the proportions of protein and fat ...
What is ketosis?
... After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves
become insufficient ... The central nervous system (CNS) cannot use fat as an energy source; hence, it normally utilizes
glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources ...
derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes
and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies
(KBs), that is, acetoacetate, ß-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs
principally in the mitochondrial matrix in the liver.
Blood levels Normal diet Ketogenic diet Diabetic ketoacidosis
Glucose (mg/dl) 80–120 65–80 >300
Insulin (µU/l) 6–23 6.6–9.4 0
KB conc (mx2133/l) 0.1 7/8 >25
pH 7.4 7.4 <7.3
We would like to emphasize that ketosis is a completely physiological mechanism and it was the biochemist Hans Krebs
who first referred to physiological ketosis to differentiate it from the pathological keto acidosis seen in type 1 diabetes.
In physiological ketosis (which occurs during very-low-calorie ketogenic diets), ketonemia reaches maximum levels of
7/8 mmol/l (it does not go higher precisely because the CNS efficiently uses these molecules for energy in place of
glucose) and with no change in pH, whereas in uncontrolled diabetic ketoacidosis it can exceed 20 mmol/l with a
concomitant lowering of blood pH.
Therapeutic roles of ketogenic diets
Strong evidence
Weight loss
1. Reduction in appetite due to higher satiety effect of proteins, effects on appetite control hormones and to a possible
direct appetite-suppressant action of the KBs.
2. Reduction in lipogenesis and increased lipolysis.
3. Reduction in the resting respiratory quotient and, therefore, greater metabolic efficiency in consuming fats.
4. Increased metabolic costs of gluconeogenesis and the thermic effect of proteins.
Cardiovascular disease
Type 2 diabetes (T2D)
... A person with insulin resistance will divert a greater proportion of dietary carbohydrate to the liver where much of it
is converted to fat, as opposed to being oxidized for energy in skeletal muscle. ... this greater conversion of dietary
carbohydrate into fat, much of it entering the circulation as saturated fat, is a metabolic abnormality that significantly
increases risk for diabetes and heart disease. Thus, insulin resistance functionally manifests itself as ‘carbohydrate
intolerance'. When dietary carbohydrate is restricted to a level below which it is not significantly converted to fat (a
threshold that varies from person to person), signs and symptoms of insulin resistance improve or often disappear
completely.
... withdrawal of insulin and major weight loss in a matter of weeks in T2D individuals who were fed a very-low-calorie
and -carbohydrate diet. ... fed obese T2D individuals two types of hypocaloric (650 kcal) diets for 3 weeks, they were
matched for protein but one was much lower in carbohydrate content (24 vs 94 g/day). As expected, the lower-
carbohydrate diet resulted in significantly greater levels of circulating ketones (~3 mmol/l), which was strongly
associated with a lower hepatic glucose output. ... higher levels of ketones are associated with more favourable effects
on glycaemic control in diabetics. ... fed a low-carbohydrate (<20 g/day) diet for 2 weeks. Plasma glucose fell from 7.5
to 6.3 mmol/l, haemoglobin A1c decreased from 7.3 to 6.8% and there were dramatic improvements (75%) in insulin
sensitivity.
T2D individuals were prescribed a well-formulated ketogenic diet for 56 weeks, and significant improvements in both
weight loss and metabolic parameters were seen at 12 weeks and continued throughout the 56 weeks as evidenced by
improvements in fasting circulating levels of glucose (-51%), total cholesterol (-29%), high-density lipoprotein–
cholesterol (63%), low-density lipoprotein–cholesterol (-33%) and triglycerides (-41%). It is of interest to note that in a
recent study in overweight non/diabetic subjects, it was reported that during ketosis fasting glucose was not affected,
but there was an elevation in post-prandial blood glucose concentration. This data suggests a different effect of ketosis
on glucose homeostasis in diabetic and non-diabetic individuals. Other studies support the long-term efficacy of
ketogenic diets in managing complications of T2D. Although significant reductions in fat mass often results when
individuals restrict carbohydrate, the improvements in glycaemic control, haemoglobin A1c and lipid markers, as well
as reduced use or withdrawal of insulin and other medications in many cases, occurs before significant weight loss
occurs. Moreover, in isocaloric experiments individuals with insulin resistance showed dramatically improved markers
of metabolic syndrome than diets lower in fat. It is interesting in this respect that a recent extremely large
epidemiological study reported that diabetes risk is directly correlated, in an apparently causative manner, with sugar
intake alone, independently of weight or sedentary lifestyle. Epilepsy
... 30–40% reduction in seizures compared with comparative controls, and the review authors reported that in children
the effects were ‘comparable to modern antiepileptic drugs'. The main drawback with the ketogenic diet was difficult
tolerability and high dropout rates ...
... The recent research reviewed here demonstrate improvements in many risk factors, such as weight, saturated fats,
inflammation and other biomarkers, as a consequence of consuming well-formulated low-carbohydrate diets ...
Emerging evidence
Acne
Cancer
There is evidence that hyperinsulinaemia, hyperglycaemia and chronic inflammation may affect the neoplastic process
through various pathways, including the insulin/IGF-1 pathway, and most cancer cells express insulin and IGF-1
receptors. Insulin has been shown to stimulate mitogenesis (even in cells lacking IGF-1 receptors)50 and it may also
contribute by stimulating multiple cancer mechanisms, including proliferation, protection from apoptotic stimuli,
invasion and metastasis.
... tumour cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin ...
Polycystic ovary syndrome (PCOS)
... symptoms include hyperandrogenism, ovulatory dysfunction, obesity, insulin resistance and subfertility.
Insulin resistance and related hyperinsulinaemia is actually a very common feature affecting about 65–70% of women
with PCOS;73 it is seen most frequently in obese patients, affecting 70–80%, compared with only 20–25% of lean PCOS
sufferers. ... Women with PCOS frequently demonstrate many of the signs related to metabolic syndrome, such as
insulin resistance, obesity, glucose intolerance, T2D, dyslipidemia and also high levels of inflammation.
... we only have preliminary evidence of the positive effects of VLCKD in PCOS...
Neurological diseases
... epilepsy, including head ache, neurotrauma, Alzheimer's and Parkinson's disease, sleep disorders, brain cancer,
autism and multiple sclerosis. ... act as neuroprotective agents by raising ATP levels and reducing the production of
reactive oxygen species in neurological tissues, together with increased mitochondrial biogenesis, which may help to
enhance the regulation of synaptic function. Moreover, the increased synthesis of polyunsaturated fatty acids
stimulated by a KD may have a role in the regulation of neuronal membrane excitability ... reducing glucose
metabolism, ketogenic diets may activate anticonvulsant mechanisms ... In addition, caloric restriction per se has been
suggested to exert neuroprotective effects, including improved mitochondrial function, decreased oxidative stress and
apoptosis, and inhibition of proinflammatory mediators, such as the cytokines tumour necrosis factor-a and
interleukins.
Alzheimer's disease
... In an animal model of Alzheimer's disease, transgenic mice consuming a ketogenic diet exhibited better
mitochondrial function and less oxidative stress and ß-amyloid deposition when compared with normally fed
controls. ...
Parkinson's disease
... typical mitochondrial respiratory chain damage that occurs in animal models of Parkinson's disease was reduced by
a ketogenic diet ...
Brain trauma
... ketogenic diet reduced post-traumatic cognitive and motor function impairment, at least in a rat model ...
Amyotrophic lateral sclerosis
The effect of a ketogenic diet on respiratory function
Potential risks of ketogenic diets
If we equate de facto ketogenic diets with high-protein diets (which is not always correct) then the risks proposed by
critics of this type of dietary approach are essentially those of possible kidney damage due to high levels of nitrogen
excretion during protein metabolism, which can cause an increase in glomerular pressure and hyperfiltration ... it
should be noted that ketogenic diets are only relatively high in protein18, 106 and that some recent studies have
demonstrated that VLCKD can even cause a regression of diabetic nephropathy in mice. With regard to possible
acidosis during VLCKD, as the concentration of KBs never rises above 8 mmol/l10 this risk is virtually inexistent in
subjects with normal insulin function.
... Further studies are warranted to investigate more in detail the potential therapeutic mechanisms, its effectiveness
and safety"
4. The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer
"KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7%
in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the
KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean
survival time compared to controls.
... While many primary tumors can be controlled with conventional therapies like surgery, chemotherapy, and
radiation, these treatments are often ineffective against metastatic disease and in some cases may promote cancer
progression and metastasis ...
Abnormal energy metabolism is a consistent feature of most tumor cells across all tissue types. In the 1930 s, Otto
Warburg observed that all cancers expressed high rates of fermentation in the presence of oxygen. This feature,
known as The Warburg Effect, is linked to mitochondrial dysfunction and genetic mutations within the cancer cell.
These defects cause cancers to rely heavily on glucose for energy, a quality that underlies the use of
fluorodeoxyglucose-PET scans as an important diagnostic tool for oncologists. Ketogenic diets are high fat, low
carbohydrate diets that have been used for decades to treat patients with refractory epilepsy. Ketogenic diets also
suppress appetite naturally thus producing some body weight loss. Dietary energy reduction (DER) lowers blood
glucose levels, limiting the energy supply to cancer cells, while elevating circulating blood ketone levels. Ketone
bodies can serve as an alternative energy source for those cells with normal mitochondrial function, but not for
cancer cells. DER has been shown to have anti-tumor effects in a variety of cancers, including brain, prostate,
mammary, pancreas, lung, gastric, and colon. DER produces anti-cancer effects through several metabolic pathways,
including inhibition of the IGF-1/PI3K/Akt/HIF-1a pathway which is used by cancer cells to promote proliferation
and angiogenesis and inhibit apoptosis. Additionally, DER induces apoptosis in astrocytoma cells, while protecting
normal brain cells from death through activation of adenosine monophosphate kinase (AMPK).
Tumors possess abnormal vasculature which blocks adequate tissue perfusion, leading to the presence of hypoxic
regions that promote chemotherapy and radiation resistance. In fact, hypoxic cancer cells are three-times more
resistant to radiation therapy than are well-oxygenated cells [48]. In addition to decreasing the efficacy of standard
care, tumor hypoxia activates a number of oncogene pathways, largely through the HIF-1 transcription factor, which
promote tumor growth, metastasis, angiogenesis, and inhibit apoptosis.
Hyperbaric oxygen therapy (HBO2T) involves administration of 100% oxygen at elevated pressure (greater than sea
level, or 1 ATA). HBO2T increases plasma oxygen saturation which facilitates oxygen delivery to the tissue
independent of hemoglobin O2 saturation. The potential benefit of using HBO2T to combat the cancer-promoting
effects of tumor hypoxia is clear. HBO2T alone has been shown to inhibit tumor growth, reduce tumor blood vessel
density, and induce the preferential expression of anti-cancer genes in rat models of mammary tumors. Additionally,
radiation and many chemotherapy drugs work by producing free radicals within the tumors, leading to cell death.
HBO2T enhances tumor-cell production of reactive oxygen species which contributes to the synergistic effects of
HBO2T as an adjuvant treatment to standard care. Indeed, HBO2T enhances the efficacy of both radiation and
chemotherapy in animal models.
... We found that the KD fed ad libitum significantly increased mean survival time in mice with metastatic cancer ... It
is important to note that KD-fed animals lost approximately 10% of their body weight over the course of the study ...
possibility that mice found the KD to be less palatable and were self-restricting caloric intake. As calorie restriction is
known to elicit profound anti-cancer effects, the ketogenic diet may inhibit cancer progression in part by indirect
dietary energy restriction ... suggesting that ketone elevation itself also contributes to the anti-cancer efficacy of the
KD ... Combining these therapies (KD with HBO2T) nearly doubled survival time in mice with metastatic cancer ...
By day 7, all animals on a ketogenic diet had significantly lower blood glucose levels than controls. As it has been
shown that tumor growth is directly correlated to blood glucose levels, this decrease in blood glucose concentration
likely contributed to the trend of decreased tumor bioluminescence and rate of tumor growth seen in KD-fed animals.
Nebeling et al. demonstrated that the KD significantly decreased glucose uptake in pediatric brain tumor patients by
FDG-PET analysis. This clinical data suggests decreased glucose delivery to the tumor is a causal mechanism in KD
treatment. All KD-fed mice showed a trend of elevated blood ketones throughout the study; however, only
KD+HBO2T mice had significantly higher ketones than controls on day 7. As ketones are metabolized exclusively
within the mitochondria, cancer cells with damaged mitochondria are unable to adequately use them for energy. ...
ketone bodies have anti-cancer effects themselves, possibly through inhibition of glycolytic enzymes ...
Potential concern may arise regarding the use of a diet therapy for cancer patients susceptible to cachexia. While low
carbohydrate or ketogenic diets promote weight loss in overweight individuals, they are also known to spare muscle
wasting during conditions of energy restriction and starvation. In an animal model of cancer cachexia, administration
of a low carbohydrate, high fat diet prevented weight loss of the animals while simultaneously decreasing tumor size.
Similar effects were described in human cancer patients ... Furthermore, when given as an adjuvant treatment to
advanced cancer patients, the KD improves quality of life and enhances the efficacy of chemotherapy treatment in
the clinic ...
It is important to look for synergistic interactions between therapies which may increase the efficacy of cancer
treatment. Scheck and coworkers reported complete remission without recurrence in 9 of 11 mice with glioma by
combining the KD with radiation. Marsh, et al. reported synergy between the restricted ketogenic diet and the
glycolysis inhibitor 2-deoxyglucose. Might adding HBO2T to these combination therapies elicit even better results?
Similarly, might the use of adjuvant therapies like KD and HBO2T enhance patient response to standard care?"
5. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.
"The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549
xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined
with carboplatin and radiation, relative to control. ... These results show that a ketogenic diet enhances radio-
chemo-therapy responses in lung cancer xenografts ..."
6. How Does the Ketogenic Diet Work? Four Potential Mechanisms
"Dietary therapies that alter the body’s energy source are effective in treating epilepsy and show promise in treating
other neurological and non-neurological conditions. These therapies include the classical ketogenic diet, a high fat,
low carbohydrate, adequate protein diet, and its variants such as the medium chain triglyceride diet, modified Atkins
diet, and low glycemic index treatment. ...
Animal and clinical studies suggest that the ketogenic diet may be useful in treating neurodegenerative diseases such
as Alzheimer, Parkinson, and amyotrophic lateral sclerosis. The diet may also limit neuronal dysfunction from
traumatic brain injury and stroke. Non-neurological conditions in which the diet may have a therapeutic role include
cancer and diabetic nephropathy. ...
... Since the ketogenic diet has anti-seizure effects, the consumption of a high fat, low carbohydrate diet ketogenic diet
must somehow alter neuronal excitability. The underlying molecular mechanisms are not fully understood ... The
proposed mechanisms reviewed here involve carbohydrate reduction, adenosine triphosphate (ATP)-sensitive
potassium channels and mitochondrial metabolism, the mammalian target of rapamycin pathway, and glutamatergic
synaptic transmission.
Carbohydrate Reduction
... All versions of the ketogenic diet including variants such as the modified Atkins diet, low glycemic index treatment,
and fasting/calorie restriction limit carbohydrates. Indeed, seizures recur within one hour of an intravenous infusion
of glucose in children with well-controlled seizures on a medium chain triglyceride diet ... The glucose analog
2-deoxy-D-glucose partially inhibits glycolysis and exerts a novel anti-seizure profile in animal models. 2-deoxy-D-
glucose is generally safe and well tolerated clinically as a tracer in positron emission studies and adjunctive therapy in
cancer trials. ...
... these results suggest that 2-deoxy-D-glucose has a unique anticonvulsant and antiepileptogenic profile, unlike that
of any currently available drug. ... However, the clinical use of 2-deoxy-D-glucose will require additional safety data
because of the association between orally administered 2-deoxy-D-glucose and cardiotoxicity in some models
Activation of ATP-sensitive potassium channels by mitochondrial metabolism
Inhibition of the mammalian target of rapamycin pathway
... This pathway responds indirectly to a variety of metabolic inputs including the insulin receptor, fasting,
ATP/adenosine monophosphate (AMP) ratio, and hypoglycemia. ... However, excessive activity of this pathway is
pathological and leads to human disorders including tuberous sclerosis complex, Cowden syndrome, and some forms of
cancer. ...
Inhibition of glutamatergic synaptic transmission
... One clinical study showed better seizure control with higher serum ß-hydroxybutyrate levels, but most other clinical
reports found no or only a transient correlation between serum ß-hydroxybutyrate or acetoacetate concentrations and
seizure control. ... Acetone has anti-seizure properties in several animal models... Accordingly, acetoacetate and ß-
hydroxybutyrate inhibit vesicular glutamate transporters ... Of the two ketones, acetoacetate is more potent, with a
half maximal inhibitory concentration less than 1 mM in physiological chloride concentrations, compared to 1–10 mM
for ß-hydroxybutyrate. ..."
7. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports.
"Two female pediatric patients with advanced stage malignant Astrocytoma tumors.
Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones
were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at
the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill
development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of
disease progression."
8. Post on a news group:
"Gloria says:
You should watch the program”Know the Cause” and follow some of the information. My husband had bladder cancer
and my son had kidney and anal cancer. I put them on the Phase l diet, gave them anti-fungals (caprylic acid, olive leaf
extract and oil of oregano w/P73). You rotate these every 3 weeks using 1 at a time. I put them on extra strength
NSC-24 beta glucan and Dr. Oh’hiras probiotics. Radiation and chemo kills you immune system, beta glucan and
probiotics put them back. You will have more energy and will not get sick. Both my husband and son are now cancer
free. You can read Doug Kaufman’s books or listen to his program to be educated."
Note: Phase 1 diet is actually not ketogenic but it is worth considering combination of some of the antifungal supplements and diet guidelines.
9. Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest.
Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.
10. Studies on ketosis
11. Utililizing a ketogenic diet to target cachexia syndrome in pancreatic cancer
12. Neuroprotective and disease-modifying effects of the ketogenic diet
13. Methylglyoxal and the Ketogenic Diet – The Miraculous Compound that got Bad-Mouthed by Ignorance
14. KETONE BODY THERAPY: From the Ketogenic Diet to the Oral Administration of Ketone Ester