Health Benefits of Ketones
A ketogenic diet is characterized by the production of ketones, small molecules that the body can use as alternative energy sources. These molecules — beta hydroxybutyrate, acetoacetate, and acetone — are produced when carbohydrate consumption is very low. Depletion of glycogen, the storage form of carbohydrate, results in the production of ketones from fatty acids.
Intermittent fasting also causes the production of ketones, since if you’re not eating anything, you’re not eating carbohydrates either.
How low does carbohydrate consumption need to be to cause the production of ketones? The amount varies, and most people will need to eat 50 grams or fewer carbohydrate daily to see a rise in ketones. People who are very physically active, such as through daily strenuous exercise, may be able to eat 100 grams or more and still be in ketosis.
Ketones are used as an alternative to glucose. The body only carries about a 24-hour supply of glycogen — which is broken down to glucose — but the supply of fat is enough to last for weeks or months, depending on how much fat the person has. So after a period of about 24 hours with minimal carbohydrate intake, the production of ketones ramps up.
Just to be clear, the ketones under discussion here have nothing to do with raspberry ketones, which are a current weight-loss fad and appear to be ineffective for that purpose.
Health benefits of ketogenic diets
Ketones and the ketogenic diet have a number of health benefits.
- The ketogenic diet has strong anti-seizure properties. Many children and adults with epilepsy, whose condition cannot be treated with drugs, become seizure-free with a ketogenic diet.(1) The effect may be due to increased mitochondrial energy production in the brain.
- Ketones and the ketogenic diet may be useful in the treatment of Alzheimer’s disease.(2) A case that was in the news not long ago was of a doctor who treated her husband’s Alzheimer’s disease with coconut oil, which metabolizes to ketones. The treatment was quite successful.(3)
- The ketogenic diet may be useful for insulin resistance.(4)
- The ketogenic diet may help treat cancer.(5) Cancer cells thrive on glucose, so keeping blood sugar low may be therapeutic.
- Finally, the ketogenic diet can be used for fat loss, the Atkins diet being a notable example.(6)
The benefits of the ketogenic diet could be due to several things, for example to the absence of carbohydrate, to the presence of ketones, a decrease in insulin, or even increased consumption of fat. Or possibly to all of these.
The absence of carbohydrate in the diet leads to lower insulin levels, and this in turn allows fat to leave fat cells and be burned as energy. Hence the fat-loss effect of low-carbohydrate diets.
As noted, after 24 hours or more of carbohydrate restriction, ketones begin to be produced, and the presence of ketones and not the absence of carbohydrate seems to be the cause of the beneficial effects of the ketogenic diet in epilepsy and Alzheimer’s.
Ketones suppress hunger
It’s also widely suspected that ketones suppress hunger. They may be the cause of the absence of hunger during prolonged fasting. Many people report that as they begin to fast, they’re hungry, but their hunger goes away as they extend their fast.
The disappearance of hunger has certainly been my experience in fasting, especially if the fast lasts more than about 16 hours. What’s probably happening is that ketone levels increase in the bloodstream, and this suppresses hunger.
The fact that many of the benefits of the ketogenic diet may be due to the ketones themselves opens the way for exogenous ketone supplements. In theory, someone could take one of these supplements to get the benefits without even restricting their carbohydrate intake.
Exogenous ketone supplements
I recently received a sample of KetoCaNa, an exogenous ketone supplement.
KetoCaNa contains beta hydroxybutyrate, one of the ketones normally produced by a ketogenic diet, and is flavored (“natural flavors”) and sweetened with stevia, a non-caloric sweetener.
I’ve used it several times now, and I can report that it works.
Works for what?
For one thing, it suppresses hunger, just as suspected. I’ve taken it several times in the morning during an intermittent fast. Hunger just goes away.
I’ve also taken it (twice) before lifting weights. Ketones may possibly be used as an alternative fuel during exercise, and thus may boost exercise performance.(7) My own experience here is less definite. Maybe it works. But the high-intensity protocol that I’ve begun practicing lately is so short — typically under 40 minutes — that I probably don’t need an alternative fuel source. I suspect that in a longer exercise bout, say cycling or running, ketones may make more of a difference. But I don’t know, since I don’t do those things.
By suppressing appetite, KetoCaNa could be useful for weight loss. Ketone supplements lead to lower body weight in rats.(8)
One drawback of KetoCaNa: the stuff is expensive. A full serving will run you over $4.00. However, half a serving seems to work well too.
The best way to use it is to take it during a fast, so ketone levels are increased. It will increase ketones if you’ve been eating as well, but that would negate many of the weight-loss benefits.
KetoCaNa may prove to be useful in treating Alzheimer’s, cancer, and epilepsy, but that remains to be seen. Most of those who take it now seem to be athletes.
There’s a newer entry into the ketone supplement line, Pruvit Keto // OS. I haven’t tried it.
Another, cheaper way to raise ketone levels is with MCT oil, which consists of medium-chain triglycerides which rapidly metabolize into ketones. MCTs seem to be difficult or impossible to store as fat, and a diet that included MCT oil resulted in significantly more fat loss than did a diet that contained olive oil, in humans.(9)
A tablespoon of MCT oil ought to do the job. Some people report stomach upset with MCT oil, but it’s never bothered me.
Another good reason to take exogenous ketones or MCT oil during an intermittent fast is because ketones stimulate autophagy, the cellular self-cleansing process.(10)
Increased autophagy is one of the main health benefits of intermittent fasting, and is mainly responsible for its longevity-promoting effect. Adding exogenous ketones while fasting ought to boost the autophagy process even more than fasting alone.
Many of the benefits of a very low carbohydrate ketogenic diet may be due to the presence of ketones. Exogenous ketone supplements can a) provide ketones even when not refraining from carbohydrates, and b) boost ketones even further when eating a ketogenic diet.
Lots of people who suffer from illnesses such as cancer or Alzheimer’s simply will not stop eating carbs. Crazy, I know, because if I had cancer I would do everything I could to treat it. But even a simple measure like cutting carbs seems beyond the reach of many. So ketone supplements may be able to fill in a gap in these cases.
Ketosis extends lifespan
Ketosis and ketone bodies
Ketone bodies are the small molecules that are produced by the liver when the body is in a state of ketosis. These can be readily used by the body and, most notably, the nervous system, and one of their functions is to spare lean tissue during ketosis, since with the burning of ketones, the body does not have to break down muscle in order to make blood glucose.
The state of ketosis is readily entered when severely restricting carbohydrates in the diet for just a short while; for instance, if someone goes on the Atkins diet, or generally keeps carbs below 50 grams a day. (If one exercises a lot or is otherwise physically active, one can eat more carbs, say up to 100 grams, and remain in ketosis.)
Ketosis extends lifespan in C. elegans
It turns out that in the roundworm C. elegans, one of the ketone bodies, beta hydroxybutyrate, extends lifespan: D-beta-hydroxybutyrate extends lifespan in C. elegans.
βHB supplementation extended mean lifespan by approximately 20%. … βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated ΒHB dehydrogenase activity and increased oxygen consumption in the worms.
So, the ketone functioned similarly to dietary restriction, increased lifespan by 20%, and caused increased metabolism.
It looks like being in ketosis much of the time could be, gasp, good for you.
The probable future Nobel Laureate Cynthia Kenyon discovered that a mutation in insulin signalling in C. elegans caused radically increased lifespan. When she made that discovery, she herself went on a low-carbohydrate diet.
So, add all this to the evidence for the healthiness of a low-carbohydrate diet.
Longer Life Through Lower Blood Sugar
Many experiments and studies on life extension have found the interesting and important result that lowering blood glucose (blood sugar) and/or restricting dietary carbohydrates means longer life. This has been found using several different lab animals and in humans as well. It’s possible to have longer life through lower blood sugar.
Acarbose is an anti-diabetic drug that works by inhibiting enzymes in the gut that break down carbohydrates to glucose, and therefore less glucose is absorbed.
Male mice that were fed acarbose lived 22% longer than controls, although the female mice lived only about 7% longer.
A lifespan increase of 22% is large, among the longer lifespan extensions seen with other interventions, comparable to rapamycin and a larger increase than fat-tissue insulin receptor knockout. Acarbose reduced fasting insulin in male mice but not in females, which may account for the difference in lifespan extension.
IGF-1 was decreased in both sexes, and fibroblast growth factor 21 (FGF21) was increased, and both of these hormonal changes could be involved in life extension.
In humans with type 2 diabetes, long-term acarbose treatment was associated with a huge 50% decrease in the risk of cardiovascular events such as heart attack and stroke. Importantly, the risk reduction was associated with a decrease in postprandial hyperglycemia, or a rise in blood sugar after eating.
A meta-analysis of acarbose found similar large reductions in CVD events.
Since dietary carbohydrates, especially grains, sugar, and starches, are the primary determinant of blood sugar, why not just cut carbohydrates instead?
Metformin is the most prescribed anti-diabetic drug, and it lowers blood sugar and insulin. Similar large reductions in death rates have been found with metformin use, so much so that diabetics using metformin may outlive non-diabetics who don’t use it.
Would cutting carbohydrates cause the same life extension and anti-aging as metformin?
An argument against that is that diabetics taking metformin may live longer than non-diabetics who don’t take it. Therefore, metformin may be causing a real anti-aging effect.
An argument for it is that most non-diabetics eat large amounts of carbohydrates, with the average American eating about 50% of his or her calories as carbohydrate. And among average people, Dr. Joseph Kraft showed that large numbers, perhaps up to 80%, have some degree of impaired glucose tolerance, i.e. they’re insulin resistant.
If metformin increased lifespan in animals or people who ate little or no carbohydrates, that would be convincing, but to my knowledge, it has not.
Glucosamine is an over-the-counter supplement commonly taken for arthritis and joint pain. Glucosamine extends lifespan in mice through
an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN [glucosamine] extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet. [My emphasis.]
Glucosamine impairs glycolysis (glucose metabolism) and therefore lowers blood glucose levels.
Glucosamine also activates autophagy, the cellular self-cleansing process that retards aging, and inhibits mTOR, the cellular growth engine that accelerates aging.
In humans, use of glucosamine is associated with an 18% lower death rate.
Again, if glucosamine mimics a low-carbohydrate diet, why not just eliminate the middleman and refrain from eating carbohydrates?
Fasting, eating a very low amount of carbohydrates (usually less than 50 grams daily), or taking ketone supplements or MCT oil raises the amount of molecules known as ketones in the bloodstream. Increased ketones mimic the effects of food restriction by lowering blood glucose and insulin.
While ketone supplements are generally beneficial in my opinion, if you cut the carbohydrates, albeit radically, you’re in ketosis (producing ketones) and presumably extending your lifespan and fighting aging by doing so.
Feeding glucose to the worm C. elegans shortens its lifespan.
Restricting glucose extends its lifespan.
When carbohydrates are digested, they become glucose inside the body, since most carbohydrates are just long chains of glucose. (Sugars may incorporate other molecules, such as fructose and galactose.)
So why not just restrict carbohydrates?
Multiple lines of evidence lead to carbohydrate restriction
As we’ve seen from the studies above, multiple lines of evidence lead to the conclusion that restricting carbohydrates and thus preventing high blood glucose, whether spikes in it or a higher average glucose, leads to longer life.
These same lines of evidence lead to the conclusion that carbohydrates can promote aging and shorten life.
Note that some carbohydrates, namely complex carbohydrates found in non-starchy vegetables, don’t raise blood sugar much if at all.
The foods that contain abundant carbohydrates and increase blood glucose are the ones to restrict or eliminate, and they include grains (wheat, rice, corn, etc.), sugar, and starchy tubers such as potatoes.
Someone who is very insulin sensitive may not be harmed much by carbohydrates. These people include athletes and other lean people who exercise or labor at physically demanding jobs.
Anyone else, and that includes most people, would likely see a big improvement in health by restricting carbohydrates.
Keto Diet Stops Cancer
Cancer is the second leading cause of death in the U.S., and is one of the most dreaded diseases anywhere. It typically strikes older people more; some 90% of cancer is diagnosed in people over the age of 50, and incidence increases with age. Could we be looking at the end of cancer?
While many of the causes of cancer have been identified, the exact manner in which cancer starts and why it does so remains an open question in science. While the lay person may consider the origin of cancer to be of academic interest only, the way that cancer starts, and even precisely what cancer is, has great relevance to prevention and treatment. A new line of thought on cancer has emerged in recent years, backed by compelling evidence, that the prevalent theory of how cancer starts and what it is are wrong, at least in part.
This new way of looking at the problem is the metabolic theory of cancer.
Is cancer caused by genetic mutations?
The prevailing theory of cancer is that it’s caused by genetic mutations, which lead to uncontrolled growth, metastasis, and death. The Mayo Clinic flatly states, “Cancer is caused by changes (mutations) to the DNA within cells.” A scholarly review, The Hallmarks of Cancer, argues that the “enabling characteristic” for these hallmarks of cancer is “genome instability”, that is, the increased propensity of the cell’s genes to mutate.
But seemingly, there’s a paradoxically low rate of mutations together with a high rate of cancer. Even the authors of the review cited above state:
But mutation of specific genes is an inefficient process, reflecting the unceasing, fastidious maintenance of genomic integrity by a complex array of DNA monitoring and repair enzymes. These genome maintenance teams strive to ensure that DNA sequence information remains pristine… Yet cancers do appear at substantial frequency in the human population, causing some to argue that the genomes of tumor cells must acquire increased mutability in order for the process of tumor progression to reach completion in several decades time.
Mutations are rare, they say, because cells strive to repair their DNA, but cancer occurs frequently.
There are a number of other paradoxes of cancer.
The discovery that cancer cells collectively manifest millions of different types of gene mutationsled to the idea that all cancers were different, or different in type, and required complex treatment.
But what if cancer cells all had a remarkable similarity, one that had nothing to do with genetic mutations?
The Warburg effect
Otto Warburg, who won the Nobel Prize for Physiology or Medicine in 1931, first proposed that cancer is due to a metabolic defect.
Just as there are many remote causes of plague, heat, insects, rats, but only one common cause, the plague bacillus, there are a great many remote causes of cancer-tar, rays, arsenic, pressure, urethane- but there is only one common cause into which all other causes of cancer merge, the irreversible injuring of respiration.
In most normal cells, energy is burned in the mitochondria in the presence of oxygen to produce ATP, the currency of energy. Cancer cells have a severely diminished, or no, capacity to do this. Instead, they burn glucose for energy in a process known as aerobic glycolysis. The mitochondria of cancer cells appear to be severely damaged, so the only way they can obtain energy is through this alternative and relatively inefficient method.
Cancer cells burn glucose, as opposed to the mixture of fat and glucose burned by normal cells. Furthermore, non-cancerous normal cells can use ketone bodies for energy, and most cancer cells cannot.
Cancer as a metabolic disease
If genetic mutations don’t cause cancer, what does?
Thomas Seyfried, the most well-known scientist in this area, postulates that cancer is a metabolic disease.
In Seyfried’s view, metabolic dysfunction in the mitochondria of cancer cells is the initial event in cancer formation. The result is genomic instability, leading to the gene mutations seen in cancer; but the mutations are not causal, the metabolic dysfunction is.
Cancer cells burn sugar as a result of their dysfunction.
Therefore, treatment partially consists of depriving cancer cells of glucose. One way to do that is to lower blood glucose levels by the ketogenic diet. In fact, Seyfried has advocated just this approach. It appears to be effective, though much more clinical research would need to be done.
2-deoxyglucose, a compound that is taken up by cells but which cannot be metabolized, and which essentially jams up the metabolic machinery, inhibits cancer cells in vitro. So it appears that depriving cancer cells of glucose, their main fuel, inhibits their growth and may kill them.
Is there any other way to jam the molecular machinery of cancer cells?
Inhibiting cancer metabolism
Enter Dr. Laurent Schwartz, French physician and oncologist, who has been working on this problem for many years and treats patients using the metabolic theory of cancer. (In addition to conventional treatment.)
Schwartz and colleagues have developed a compound called Metabloc, which consists of two over-the-counter (in the U.S. at least) supplements, hydroxycitrate and alpha lipoic acid. These two compounds interfere with the metabolism of cancer cells, but have little effect on the metabolism of normal cells. Below is a chart showing various strengths of both compounds either alone or in combination against cancer cells in vitro. The highest concentrations of the combination, though still in the micromolar range, reduced cancer cell viability to zero, i.e. no surviving cells.
This treatment, in contrast to standard cancer treatment, is non-toxic, with few side effects.
In vivo, in mice, the combination works too, greatly inhibiting tumor growth. Interestingly, adding another common compound, capsaicin, the substance that gives hot chili peppers their heat, inhibited cancer cells even more. The addition of a fourth compound, a peptide drug called octreotide, further diminished cancer cell viability. Octreotide is a potent inhibitor of growth hormone.
Schwartz has published several papers on the effects in actual patients; the most recent (as far as I know) is “Combination of Metabolic Treatment of Aggressive Primary Brain Tumour and Multiple Metastases of the Brain”.
Background: The combination of hydroxycitrate and lipoic acid has been demonstrated by several laboratories to be effective in reducing murine cancer growth. In previous article in 2014, we reported the fate of 11 patients treated for metastatic cancer unresponsive to chemotherapy. As of today, 32 months after inclusion, five of these patients (45%) are still alive.
Patients and Methods: We report the cases of 12 patients with advanced brain tumor. They were all treated with conventional treatment and a combination of sodium R lipoate (800 mg bid), hydroxycitrate at 500 mg tid and low-dose naltrexone at 5 mg at bedtime. Eight patients had primary brain tumour (n=8 including five glioblastomas) four patients had multiple brain metastases.
Results and Discussion: The combination of conventional and metabolic treatment was well tolerated. Four out of five patients with gliobastoma are still alive and well. The longest follow-up is 7 years.The four patients with disease widely metastatic to the brain have experienced long-term survival. A randomized clinical trial of metabolic treatment associated with conventional treatment is warranted.
The conclusion of the paper states:
To our knowledge, this is the first attempt to treat cancer using a combination of molecules targeting abnormal cancer metabolism. None of these patients experienced major side effects of metabolic treatment. At this stage of development, not a single case proves the efficacy of treatment. But at the time of writing, most patients were alive and well several months after having been sent home to await their death. Several months of life without symptoms strongly suggests that targeting cancer metabolism may be a reasonable option in therapy of advanced brain cancer. The role of metabolic treatment and its association with existing therapy remains to be explored in well-conducted trials.
The end of cancer?
It’s obviously too soon to say whether this new treatment for cancer will be so much of a success that the treatment becomes widely accepted and used. Apparently, Dr. Schwartz is the only oncologist in the world who is using it. His new book is “Cancer: Un Traitement Simple et Non Toxique.”
The number of cancers is increasing and, despite what we hear about medical progress, mortality has not dropped since 1960 , especially for tumors of the pancreas, lungs, liver, brain …
And if, instead of merely seeking to destroy cancer cells with aggressive treatments, they were also rendered functional again? This approach can improve the effectiveness of chemotherapy and the survival of patients.
This is the conviction of Dr. Laurent Schwartz, shared by many scientists around the world. This brilliant physician and researcher in cancer has spent his career gathering evidence that the mechanisms that cause cells to multiply in an anarchic way are essentially related to a sugar burning problem .
In this book written for patients and caregivers, he proposes to normalize the metabolism of cancer cells by a combination of non-toxic and inexpensive foods and supplements, or even a diet low in carbohydrates.
This metabolic treatment has already benefited many patients.
I can only say that if I had cancer, I would definitely seek out the expertise of Laurent Schwartz. He appears to be little known in the U.S., but his latest book will be translated into English and published here. It’s also being translated into Spanish and Italian.
Dr. Laurent Schwartz
While Dr. Schwartz has patented Metabloc, the fact that it’s comprised of two OTC supplements means it’s cheap and that huge pharmaceutical industry profits can’t be made on this treatment. That’s an obstacle to it becoming more widely adopted, since cancer treatment is big business
More Muscle Gains and Fat Loss on a Ketogenic Diet
What happens when you combine weight lifting with a very low carbohydrate ketogenic diet(VLCKD)? You get greater muscle gains and more fat loss than when compared to a conventional diet.
The study looked at a group of “college aged resistance trained men”, and put them on either a conventional Western diet or a VLCKD.
The conventional diet was 55% carbohydrate, 25% fat, and 20% protein, similar to what lots of people eat, though a bit higher in protein, a bit lower in fat.
The low-carb diet was 5% carbohydrate, 75% fat, and 20% protein.
Note that protein, the main macronutrient responsible for muscle growth, was the same in both groups. Both groups did resistance training three times a week for 11 weeks.
The very low carbohydrate group gained twice as much muscle as the conventional group, 4.3 kg vs 2.2 kg.
The very low carbohydrate group lost 50% more fat than the conventional group, -2.2 kg vs -1.5 kg.
It should be noted that this is from a “poster presentation” at a conference, and as such has not been peer-reviewed.
What could be going on here? The extra fat loss was not a surprise to me. Low-carbohydrate diets have a much better record at fat loss than do conventional diets. However, this was not a weight-loss trial, and presumably the participants ate as much as they wanted.
How ketogenic diets could increase muscle gains
There are several ways that muscle gains could be greater when a ketogenic diet is combined with weight training.
- Adrenergic stimulation. Lower blood glucose (sugar) stimulates adrenaline release, which inhibits muscle protein breakdown. Although this doesn’t directly relate to gains, the breakdown of muscle is a normal, daily occurrence in healthy people, for instance with overnight fasting. Inhibiting this could mean greater gains.
- Ketone bodies produced by the VLCKD inhibit muscle breakdown. However, carbohydrate ingestion does this also, so perhaps this aspect is a wash.
- Growth hormone. Lower blood glucose means an increase in growth hormone. As carbohydrate does not increase growth hormone, this could be a major factor in better gains and fat loss.
- Dietary protein. Generally, people ingest more protein on a low-carb diet, resulting in increased muscle mass. However, the protein consumption here was the same in both groups.
Most bodybuilders will tell you that you need carbohydrates to build muscle, or that it’s more effective with carbohydrates, but there are several reasons for thinking that is not the case
Protein alone and not carbohydrate is responsible for muscle growth and, once the metabolism is adapted to burning fat, intense exercise can be performed on a low-carb diet.
One reason for thinking that carbohydrates make for better gains, and this may be a real consideration, is that people often spontaneously decrease calorie intake on a very low-carbohydrate diet. This may account for much of this diet’s efficacy in fat loss. But if you’re looking for those gains, you need to eat enough, and it could be that many low-carb eaters do not.
But it seems for most people a VLCKD could be just the ticket for muscle gains and fat loss when combined with regular resistance training.