Category: Health

A very interesting week! I discovered the pivotal relationship between protein and ketosis, and finally saw a reduction in my appetite.

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

This post is part of a series describing my attempt to follow Dr. Seyfried’s dietary recommendations for cancer. To start at the beginning, please go to the first post: “Seyfried’s Ketogenic Cancer Diet: My Fasting Jump-Start to Ketosis.“

Traveling on a ketogenic diet

Being in Salt Lake City from Day 7 to Day 11 was challenging. I had no car, no grocery store, no microwave . . . I was completely at the mercy of hotel, conference, and restaurant food. Luckily I had a great pocket-sized travel scale (made by Salter) to help me out, but most of the meats I ate while away were not my usual fare. I did my best!

Day 8 (2/7/13)

Notes: Very hungry with mild headache first thing in the morning and again at midday, but no appetite at dinnertime.

Day 9 (2/8/14)

Notes: Very hungry with mild headache in the morning. Forgot my scale today while out and about, so overshot my protein grams.

Day 10 (2/9/13)

Notes: This was the first morning that I wasn’t extremely hungry with a headache first thing in the morning—I felt fine. Overshot protein again. Appetite much lower all day. After snowshoeing, when everyone else felt hungry, food did not even interest me. Easily sat in an ice cream/chocolate cafe with other people without any temptation whatsoever.

Now that my appetite has come down and I’ve completed seven full days on my original plan of ~75 g protein (yet continue to see high blood glucose levels and only modest blood ketones), it’s time to adjust the plan.

NEW PLAN: Continue max carbs 30 but reduce protein to see if I can get ketones up to at least 4.0 mM and blood glucose down into the 60’s (Seyfried’s “zone of metabolic management”).

Day 11 (2/10/13)

Notes: Mild headache in the morning but appetite low today. Flew back to Boston from Utah. Finally home where I have total control over food choices.

Day 12 (2/11/13)

Notes: Sleep light, eyes feel dry (this always happens when I eat olives). Hungry mid-day and at 8 pm, but not ravenous. Very sleepy from 12:30 to 1:30. Queasy early evening. I don’t know if it was the extra fat intake and/or the guacamole itself which caused the sleepiness and queasiness.

Ketones and blood sugar clearly seem to care most about protein grams (as some of you had commented), and it is interesting to see how rapidly the ketones responded to the reduction in protein intake. This gives me hope that If I lower protein even more, the ketones and blood sugar will fall into range quickly.

Day 13 (2/12/13)

Notes: Sleep light, eyes dry, mild tinnitus (ringing in ears), but felt better within an hour of waking. I got hungry at lunchtime, so I eyed the 2 little lamb chops in my fridge. I thought to myself: “there is no way that those 2 wee lamb chops are going to do the trick.” Even worse, when I calculated how much protein I could have for lunch, I realized I should only eat ONE of these mini-meats. I cooked only one of them, and stared at its teeny tiny-ness, feeling like I could have easily eaten TEN of them. But I ate just the one, and within 10 minutes I was not hungry any more. Wow. Sleepy late afternoon and took a nap.

I was aiming for 50 g protein today to see if I could get ketones up to 4.0. I didn’t realize that the avocado contained protein, so overshot by 4 grams.

Day 14 (2/13/13)

Notes: Mild headache and dry eyes in the morning (I should really get rid of the olives . . . but they are so helpful—they have no protein, and are very low-carb and very high fat).

Reflections on week 2

Protein and ketosis

While it’s still early in this experiment, it seems that protein grams are an important driver of ketone levels—not calories, not fat grams, not protein to fat ratios. I am happy to see that I don’t need to eat MCT oil (which I’ve heard can cause gastrointestinal side effects in some people), palm fruit oil (which I know I don’t like or tolerate well), or increase fat grams any more to achieve high ketone levels. Some of you very smart people who are experienced with ketogenic diets were begging me to lower my protein intake sooner, and you were clearly right, but I was in no hurry with this experiment and wanted to wait at least a whole week to observe my own patterns. I also wanted to stick with the protein intake recommended by the “experts” in the field for a full week to see if it would work for me, but clearly my ideal protein intake is lower than that recommended by some experts. I was also too hungry during Week 1 to even think about eating less protein . . .

Appetite and ketosis

Appetite level was very unstable during Week 1 but really came down during Week 2. On the final day of Week 2, I was perfectly satisfied eating less than 1000 calories. I wasn’t even trying to limit my calories that day, I just happened not to want any more food.

With appetite so much lower, I’m hoping I can cut back on the salads, because I feel better when I eat mostly meat.

Calories and ketosis

I suspect that if I were to raise my calories by raising my fat intake, I would stop losing weight, but some of you have said that this isn’t true and that I should eat a lot more fat. At least right now, I have no desire to eat any more than I’m eating, and my ketone levels are nice and high, so I feel no need to raise my fat intake. My logic tells me that if I eat more fat, my body will burn more of that fat and therefore burn less excess body fat, which is the goal.

However, I would like to experiment with this once I’m fully keto-adapted. After I’ve been in ketosis for a full month, maybe I will try adding in more fat calories just to see what happens. Or, if I get hungry, I will add more fat, of course. I have no desire to be hungry on this plan—after all, one of the benefits of a ketogenic diet is supposed to be excellent appetite control.

What does this experiment mean for cancer patients?

Of course this is just my own personal experience, and yours may be very different. I am hopeful that cancer patients may be able to rapidly achieve Seyfried’s “zone of metabolic management” by strict protein and carbohydrate limitation rather than fasting. It does not appear as if calorie restriction is necessary, as he suggests (based on his mouse experiments). My ketones rose nicely regardless of how many calories I ate.

Dairy and ketosis

Keep in mind that I’m not eating dairy products, which can raise insulin levels (see my dairy page), and therefore interfere with deep ketosis. So, if you limit your protein and carbs but are eating a lot of cheese, heavy cream, sour cream, etc. and you find your ketones are not rising enough, you may want to eliminate dairy for a few days to see if that helps.

Goals for the coming week

• To further explore the relationship between fat grams, calories, and ketosis
• To eliminate olives and the new vinaigrette to see if energy, sleep quality, bloating, and mild morning headaches improve.
• To try to maintain blood ketones at 4.0 or higher
• To bring morning and evening blood sugars into the 55 to 65 mg/dL range and keep them there. What will I need to do to achieve this? I don’t think I should lower protein or calories any further. . . . Will I need to increase exercise? Get rid of all plant foods? [Plant foods = carbs]. I have always felt best when I eat no plants at all, but while adjusting to the ketogenic diet I was pretty hungry and had to eat something . . .

To see if I was able to reach any of these goals, please see the next post in this series: “Keto for Cancer: Week 3—Being Sick on a Ketogenic Diet.“ If you are interested in starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

A very interesting week! I discovered the pivotal relationship between protein and ketosis, and finally saw a reduction in my appetite.

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

This post is part of a series describing my attempt to follow Dr. Seyfried’s dietary recommendations for cancer. To start at the beginning, please go to the first post: “Seyfried’s Ketogenic Cancer Diet: My Fasting Jump-Start to Ketosis.“

Traveling on a ketogenic diet

Being in Salt Lake City from Day 7 to Day 11 was challenging. I had no car, no grocery store, no microwave . . . I was completely at the mercy of hotel, conference, and restaurant food. Luckily I had a great pocket-sized travel scale (made by Salter) to help me out, but most of the meats I ate while away were not my usual fare. I did my best!

Day 8 (2/7/13)

Notes: Very hungry with mild headache first thing in the morning and again at midday, but no appetite at dinnertime.

Day 9 (2/8/14)

Notes: Very hungry with mild headache in the morning. Forgot my scale today while out and about, so overshot my protein grams.

Day 10 (2/9/13)

Notes: This was the first morning that I wasn’t extremely hungry with a headache first thing in the morning—I felt fine. Overshot protein again. Appetite much lower all day. After snowshoeing, when everyone else felt hungry, food did not even interest me. Easily sat in an ice cream/chocolate cafe with other people without any temptation whatsoever.

Now that my appetite has come down and I’ve completed seven full days on my original plan of ~75 g protein (yet continue to see high blood glucose levels and only modest blood ketones), it’s time to adjust the plan.

NEW PLAN: Continue max carbs 30 but reduce protein to see if I can get ketones up to at least 4.0 mM and blood glucose down into the 60’s (Seyfried’s “zone of metabolic management”).

Day 11 (2/10/13)

Notes: Mild headache in the morning but appetite low today. Flew back to Boston from Utah. Finally home where I have total control over food choices.

Day 12 (2/11/13)

Notes: Sleep light, eyes feel dry (this always happens when I eat olives). Hungry mid-day and at 8 pm, but not ravenous. Very sleepy from 12:30 to 1:30. Queasy early evening. I don’t know if it was the extra fat intake and/or the guacamole itself which caused the sleepiness and queasiness.

Ketones and blood sugar clearly seem to care most about protein grams (as some of you had commented), and it is interesting to see how rapidly the ketones responded to the reduction in protein intake. This gives me hope that If I lower protein even more, the ketones and blood sugar will fall into range quickly.

Day 13 (2/12/13)

Notes: Sleep light, eyes dry, mild tinnitus (ringing in ears), but felt better within an hour of waking. I got hungry at lunchtime, so I eyed the 2 little lamb chops in my fridge. I thought to myself: “there is no way that those 2 wee lamb chops are going to do the trick.” Even worse, when I calculated how much protein I could have for lunch, I realized I should only eat ONE of these mini-meats. I cooked only one of them, and stared at its teeny tiny-ness, feeling like I could have easily eaten TEN of them. But I ate just the one, and within 10 minutes I was not hungry any more. Wow. Sleepy late afternoon and took a nap.

I was aiming for 50 g protein today to see if I could get ketones up to 4.0. I didn’t realize that the avocado contained protein, so overshot by 4 grams.

Day 14 (2/13/13)

Notes: Mild headache and dry eyes in the morning (I should really get rid of the olives . . . but they are so helpful—they have no protein, and are very low-carb and very high fat).

Reflections on week 2

Protein and ketosis

While it’s still early in this experiment, it seems that protein grams are an important driver of ketone levels—not calories, not fat grams, not protein to fat ratios. I am happy to see that I don’t need to eat MCT oil (which I’ve heard can cause gastrointestinal side effects in some people), palm fruit oil (which I know I don’t like or tolerate well), or increase fat grams any more to achieve high ketone levels. Some of you very smart people who are experienced with ketogenic diets were begging me to lower my protein intake sooner, and you were clearly right, but I was in no hurry with this experiment and wanted to wait at least a whole week to observe my own patterns. I also wanted to stick with the protein intake recommended by the “experts” in the field for a full week to see if it would work for me, but clearly my ideal protein intake is lower than that recommended by some experts. I was also too hungry during Week 1 to even think about eating less protein . . .

Appetite and ketosis

Appetite level was very unstable during Week 1 but really came down during Week 2. On the final day of Week 2, I was perfectly satisfied eating less than 1000 calories. I wasn’t even trying to limit my calories that day, I just happened not to want any more food.

With appetite so much lower, I’m hoping I can cut back on the salads, because I feel better when I eat mostly meat.

Calories and ketosis

I suspect that if I were to raise my calories by raising my fat intake, I would stop losing weight, but some of you have said that this isn’t true and that I should eat a lot more fat. At least right now, I have no desire to eat any more than I’m eating, and my ketone levels are nice and high, so I feel no need to raise my fat intake. My logic tells me that if I eat more fat, my body will burn more of that fat and therefore burn less excess body fat, which is the goal.

However, I would like to experiment with this once I’m fully keto-adapted. After I’ve been in ketosis for a full month, maybe I will try adding in more fat calories just to see what happens. Or, if I get hungry, I will add more fat, of course. I have no desire to be hungry on this plan—after all, one of the benefits of a ketogenic diet is supposed to be excellent appetite control.

What does this experiment mean for cancer patients?

Of course this is just my own personal experience, and yours may be very different. I am hopeful that cancer patients may be able to rapidly achieve Seyfried’s “zone of metabolic management” by strict protein and carbohydrate limitation rather than fasting. It does not appear as if calorie restriction is necessary, as he suggests (based on his mouse experiments). My ketones rose nicely regardless of how many calories I ate.

Dairy and ketosis

Keep in mind that I’m not eating dairy products, which can raise insulin levels (see my dairy page), and therefore interfere with deep ketosis. So, if you limit your protein and carbs but are eating a lot of cheese, heavy cream, sour cream, etc. and you find your ketones are not rising enough, you may want to eliminate dairy for a few days to see if that helps.

Goals for the coming week

• To further explore the relationship between fat grams, calories, and ketosis
• To eliminate olives and the new vinaigrette to see if energy, sleep quality, bloating, and mild morning headaches improve.
• To try to maintain blood ketones at 4.0 or higher
• To bring morning and evening blood sugars into the 55 to 65 mg/dL range and keep them there. What will I need to do to achieve this? I don’t think I should lower protein or calories any further. . . . Will I need to increase exercise? Get rid of all plant foods? [Plant foods = carbs]. I have always felt best when I eat no plants at all, but while adjusting to the ketogenic diet I was pretty hungry and had to eat something . . .

To see if I was able to reach any of these goals, please see the next post in this series: “Keto for Cancer: Week 3—Being Sick on a Ketogenic Diet.“ If you are interested in starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

A bumpy transition to ketosis

Fasting for more than 36 hours proved challenging in ways that took me completely by surprise so I decided to break my fast on Day 4 and continue my transition to ketosis while eating food. My goal remains to reach Prof. Seyfried’s recommended “zone of metabolic management”: blood glucose between 55 and 65 mg/dL and blood ketone levels of at least 4.0 mM. How much protein should I eat to try to get there? How many calories?

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

This post is part of a series describing my attempt to follow Dr. Seyfried’s dietary recommendations for cancer. To see what happened on Days 1-3, please go to the first post: “Seyfried’s Ketogenic Cancer Diet: My Fasting Jump-Start to Ketosis.”

A funny thing happened on the way to ketosis . . .

Day 4 (2/3/13)—fourth day of fasting

Notes: Only slept from 2 am to 5:30 am. Big jump in ketones this morning, but hungrier. Numerous unhappy symptoms: difficulty concentrating, tired but couldn’t sleep, mild headache, low energy, a little cold, heartbeat a little stronger than usual, dark circles under eyes, stomach growly, and slight tinnitus (ringing in the ears). At this point, I considered breaking the fast, but then something happened that convinced me it was time to eat.

My cell phone rang at about 2 pm [my ringtone is a harp playing a lovely arpeggio; you may be familiar with it]. Anyway, I answered the call, spoke for a few minutes, and then hung up. But the harp kept playing, very faintly and mysteriously, in the distance, nowhere near where my phone was located . . . over and over again. Uh-oh. I realized that I must be having a mild auditory hallucination—certainly something I had never experienced before in my whole life. While absolutely fascinating to me on one level, it was a clear indication that my brain was not getting the nutrients it needed to function properly, so quite concerning on another level.

This hauntingly beautiful harp call was either a sign that my ascension was drawing nigh, or it was time to have some lunch. I chose lunch:)

What does this mean for cancer patients?

What does this mean for people with cancer who may have been considering fasting up to 5 days to rapidly establish ketone levels of 4.0 mM? It may mean nothing. It may be my own unique response to fasting. Perhaps some people tolerate fasting for more than 3 days beautifully. However, at least for me, fasting for longer than 3 days was not tolerable, and to have continued the fast would have been unwise.

Now, if I had continued another day or two until my ketones had risen to 4.0 mM, would all of the side effects have gone away? I don’t know. If I had already been keto-adapted (at lower ketone levels), would I have tolerated the fast better? Maybe, I don’t know. But since the point of the fast is to change from a regular diet to ketosisk as rapidly as possible, people who try this plan aren’t expected to be keto-adapted already. In most cases, I think it may be wiser to try Dr. Seyfried’s alternative initiation plan instead of fasting (see details in the “Dietary Treatment of Cancer” post).

I certainly could never have accomplished his recommendation of an annual 7-day fast, so my cells will not have the opportunity to cannibalize each other after all. I am just going to have to hope that my healthy diet naturally reduces my risk for developing pre-cancerous cells in the first place.

The transition to a ketogenic diet

What’s next? I will continue to try to reach Seyfried’s “zone of metabolic management” while eating a carefully measured, mostly meat, ketogenic diet.

First, I need to calculate my protein requirements. Based on my personal stats:

• Dr. Seyfried recommends I eat between 62 and 92 grams of protein per day.
• Phinney and Volek recommend I eat between 75 and 156 grams of protein per day.
• Dr. Rosedale recommends I eat 77 grams of protein per day based on my body measurements, but 47 grams of protein per day based on my body fat percentage.

Hmmmm . . . since protein requirements are clearly difficult to estimate (see my protein page for more details), and one size does not fit all, I’m just going to start with 75 grams of protein per day, and if I need to adjust it along the way, I will.

If I were trying to treat cancer, Dr. Seyfried would want me to reduce my calorie intake significantly below my daily requirements (resting/basal metabolic rate or “BMR”). My estimated BMR is 1400 cals/day, so I’ll try to keep my calories to a maximum of 1400 per day.

Day 4, continued:

Notes: I felt much better about an hour after eating some food. It was especially wonderful to regain my powers of concentration. And surprisingly, despite having not eaten a thing for nearly 4 days, once I started eating, my appetite was actually fairly low. Therefore my calories for the day were also pretty low. Was this the effect of high ketone levels/low insulin levels?

Day 5 (2/4/13)

Notes: Got very hungry at dinnertime but a very small amount of food was required to feel better (8 g protein + 13 g fat).

Reflections on my transition to ketosis, week 1

• Fasting certainly does jump-start ketosis, but fasting for more than 36 hours may not be safe for everyone, and was no fun.
• Appetite is generally much lower as ketones rise.
• Hunger feels different in ketosis than on a standard diet. I experienced mild headache, stomach growls, calm thoughts of food, can still go hours without eating and function fine. Zero emotional component. Compare this to hunger on a standard diet, which (for me) = irritability, anxiety, distractibility, emotional longing for food, sense of urgency, carbohydrate cravings, and wish to stop whatever I’m doing and find something to eat right away.
• My blood sugar is still pretty high despite high ketones, but I think all bets are off during first few weeks, as “keto-adaptation” can take 3 weeks or more. [Keto-adaptation refers to the body’s adjustment to the efficient use of ketones for fuel instead of glucose.]
• Do I need to eat more fat to get higher ketones, or is it just a matter of time? If I were to eat more fat, that would mean more calories—would weight loss slow down or stop?
• I am hesitant to do any experiments within my experiment until after a month of this plan, so for now I’m going to stick with: 75 g protein, 1400 cals max, carbs less than 30 g/day, mostly meat, no dairy, no caffeine, no artificial anything.

Check out “Keto for Cancer: Week 2—Protein and Ketosis” to see how I got my ketones way, way up. For information about starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

A bumpy transition to ketosis

Fasting for more than 36 hours proved challenging in ways that took me completely by surprise so I decided to break my fast on Day 4 and continue my transition to ketosis while eating food. My goal remains to reach Prof. Seyfried’s recommended “zone of metabolic management”: blood glucose between 55 and 65 mg/dL and blood ketone levels of at least 4.0 mM. How much protein should I eat to try to get there? How many calories?

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

This post is part of a series describing my attempt to follow Dr. Seyfried’s dietary recommendations for cancer. To see what happened on Days 1-3, please go to the first post: “Seyfried’s Ketogenic Cancer Diet: My Fasting Jump-Start to Ketosis.”

A funny thing happened on the way to ketosis . . .

Day 4 (2/3/13)—fourth day of fasting

Notes: Only slept from 2 am to 5:30 am. Big jump in ketones this morning, but hungrier. Numerous unhappy symptoms: difficulty concentrating, tired but couldn’t sleep, mild headache, low energy, a little cold, heartbeat a little stronger than usual, dark circles under eyes, stomach growly, and slight tinnitus (ringing in the ears). At this point, I considered breaking the fast, but then something happened that convinced me it was time to eat.

My cell phone rang at about 2 pm [my ringtone is a harp playing a lovely arpeggio; you may be familiar with it]. Anyway, I answered the call, spoke for a few minutes, and then hung up. But the harp kept playing, very faintly and mysteriously, in the distance, nowhere near where my phone was located . . . over and over again. Uh-oh. I realized that I must be having a mild auditory hallucination—certainly something I had never experienced before in my whole life. While absolutely fascinating to me on one level, it was a clear indication that my brain was not getting the nutrients it needed to function properly, so quite concerning on another level.

This hauntingly beautiful harp call was either a sign that my ascension was drawing nigh, or it was time to have some lunch. I chose lunch:)

What does this mean for cancer patients?

What does this mean for people with cancer who may have been considering fasting up to 5 days to rapidly establish ketone levels of 4.0 mM? It may mean nothing. It may be my own unique response to fasting. Perhaps some people tolerate fasting for more than 3 days beautifully. However, at least for me, fasting for longer than 3 days was not tolerable, and to have continued the fast would have been unwise.

Now, if I had continued another day or two until my ketones had risen to 4.0 mM, would all of the side effects have gone away? I don’t know. If I had already been keto-adapted (at lower ketone levels), would I have tolerated the fast better? Maybe, I don’t know. But since the point of the fast is to change from a regular diet to ketosisk as rapidly as possible, people who try this plan aren’t expected to be keto-adapted already. In most cases, I think it may be wiser to try Dr. Seyfried’s alternative initiation plan instead of fasting (see details in the “Dietary Treatment of Cancer” post).

I certainly could never have accomplished his recommendation of an annual 7-day fast, so my cells will not have the opportunity to cannibalize each other after all. I am just going to have to hope that my healthy diet naturally reduces my risk for developing pre-cancerous cells in the first place.

The transition to a ketogenic diet

What’s next? I will continue to try to reach Seyfried’s “zone of metabolic management” while eating a carefully measured, mostly meat, ketogenic diet.

First, I need to calculate my protein requirements. Based on my personal stats:

• Dr. Seyfried recommends I eat between 62 and 92 grams of protein per day.
• Phinney and Volek recommend I eat between 75 and 156 grams of protein per day.
• Dr. Rosedale recommends I eat 77 grams of protein per day based on my body measurements, but 47 grams of protein per day based on my body fat percentage.

Hmmmm . . . since protein requirements are clearly difficult to estimate (see my protein page for more details), and one size does not fit all, I’m just going to start with 75 grams of protein per day, and if I need to adjust it along the way, I will.

If I were trying to treat cancer, Dr. Seyfried would want me to reduce my calorie intake significantly below my daily requirements (resting/basal metabolic rate or “BMR”). My estimated BMR is 1400 cals/day, so I’ll try to keep my calories to a maximum of 1400 per day.

Day 4, continued:

Notes: I felt much better about an hour after eating some food. It was especially wonderful to regain my powers of concentration. And surprisingly, despite having not eaten a thing for nearly 4 days, once I started eating, my appetite was actually fairly low. Therefore my calories for the day were also pretty low. Was this the effect of high ketone levels/low insulin levels?

Day 5 (2/4/13)

Notes: Got very hungry at dinnertime but a very small amount of food was required to feel better (8 g protein + 13 g fat).

Reflections on my transition to ketosis, week 1

• Fasting certainly does jump-start ketosis, but fasting for more than 36 hours may not be safe for everyone, and was no fun.
• Appetite is generally much lower as ketones rise.
• Hunger feels different in ketosis than on a standard diet. I experienced mild headache, stomach growls, calm thoughts of food, can still go hours without eating and function fine. Zero emotional component. Compare this to hunger on a standard diet, which (for me) = irritability, anxiety, distractibility, emotional longing for food, sense of urgency, carbohydrate cravings, and wish to stop whatever I’m doing and find something to eat right away.
• My blood sugar is still pretty high despite high ketones, but I think all bets are off during first few weeks, as “keto-adaptation” can take 3 weeks or more. [Keto-adaptation refers to the body’s adjustment to the efficient use of ketones for fuel instead of glucose.]
• Do I need to eat more fat to get higher ketones, or is it just a matter of time? If I were to eat more fat, that would mean more calories—would weight loss slow down or stop?
• I am hesitant to do any experiments within my experiment until after a month of this plan, so for now I’m going to stick with: 75 g protein, 1400 cals max, carbs less than 30 g/day, mostly meat, no dairy, no caffeine, no artificial anything.

Check out “Keto for Cancer: Week 2—Protein and Ketosis” to see how I got my ketones way, way up. For information about starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

Dr. Seyfried’s book, Cancer as a Metabolic Disease, inspired me to attempt a fasting jump-start to ketosis to see how long it takes to achieve his “zone of metabolic management.” Read on to see how it’s going so far! (I’m still alive . . . )

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

Dr. Seyfried’s ketogenic diet for cancer

Caution: dietary experiments with fasting and ketosis are best done under medical supervision, particularly if you have a medical condition or take any daily medications. Everyone’s metabolism is different, so results will vary. Please see my post “Is the Ketogenic Diet Safe for Everyone?“

After reading Dr. Seyfried’s book,1 I immediately felt sympathy for those of you out there who have cancer now, or who are cancer survivors worried about recurrence—were you hoping for a simple nutritional strategy, such as “eat more broccoli” or “add chia seeds to your morning smoothie?” Had I led you down a road of hope and then left you feeling disheartened when you saw how difficult Dr. Seyfried’s diet appeared to be? Let me try to make it up to you by trying his diet myself while you watch from the comfort of your living room.

Seyfried’s fasting jump-start to ketosis

Dr. Seyfried says the fastest way to achieve optimal blood glucose and ketone levels is to begin with a water-only fasting jump-start to ketosis for 3-5 days. Then embark on a low-calorie “ketogenic” diet, aiming for blood sugar levels of 55-65 mg/dL and blood ketone levels of at least 4.0 mM (see article 3 of my cancer series for more details). As a reminder, average blood glucose levels for most healthy people eating a standard diet run between about 70 and 95 mg/dl, and blood ketone levels are usually 0.3 mM or less.

His plan sounded extreme even to me. However, fasting is supposed to be rather comfortable once you get used to it, and ketogenic diets are known for reducing appetite and improving people’s sense of well-being in most cases. Thankfully I do not have cancer, but nevertheless, in an attempt to rekindle the hope that some of you may have lost, I thought I’d take one for the team and try his recommendations myself.

Goals of this experiment

• To see if I can reach Dr. Seyfried’s “zone of metabolic management.”
• To see if I can maintain high ketone levels and low blood sugar levels using my mostly-meat diet [standard ketogenic diets tend to rely heavily on high-fat dairy products, eggs, and coconut oil, none of which I tolerate well].
• To explore the impact of protein: fat ratios, calories, and exercise on ketone and blood sugar levels.
• To compare urine ketones to blood ketones and see if there is any correlation.
• To document effect of this diet on mood, energy, concentration, weight, sleep, etc.
• To document any side effects of this diet.

My N=1 experiment, phase I: fasting jump-start to ketosis

“N=1” refers to an experiment with only one subject (in this case, me). Everyone’s metabolism is different, so please take my experience with a big grain o’ salt. Please note that, just because Dr. Seyfried suggests that a water-only fast is the fastest way to get into ketosis does not mean that it is required. I also can’t say whether faster is necessarily better for your health or easier than a gradual transition to ketosis.

Supplies:

Note on the ketone meter: When I conducted this experiment, the most affordable, accurate ketone meter was the Precision Xtra®. Unfortunately the “affordable” ketone strips cost $2.22 each! I have since found a meter just as accurate, with an array of great features—and the strips are a much more reasonable 99 cents. You can read more about why I recommend the Keto-Mojo glucose/ketone meter on my ketogenic diet and mental health resources page. Because I like their meter and their mission, I’ve partnered with them to offer my readers 15% off of the purchase of any new meter kit. Just click the link here; no coupon code necessary.

Day 1 (1/31/13)

Notes: Much easier day than I had expected. Stomach a little growly, slightly lightheaded, minor difficulty concentrating, vision slightly blurry, low energy. Slept well, but had a funny dream about a granola bar—something I haven’t eaten in nearly six years! Since exercise confuses things, none for now.

Day 2 (2/1/13)

Notes: Fascinating that blood sugar this morning was higher than last night, without any food. This may be due to cortisol and adrenaline reactions to falling blood sugar—these hormones kick in when blood sugar falls to pull it back up again. Mild headache in the morning. More difficulty concentrating today—”spacey” would be the right word—but it only affected my efficiency in doing paperwork. I was otherwise fine and able to work a full day, run errands, drive, etc. Sleep was terrible—slept from 10pm to 1:30 am, then wide awake until 5am, then back to sleep until about 7:30 am. Sleep quality itself was very light and dream-filled, but no granola bar visions tonight. I can’t believe how much easier this is than I thought it would be—I’m not experiencing distressing levels of hunger or cravings.

Day 3 (2/2/13—Happy Groundhog’s Day!)

Notes: Finally, we have the appearance of (modest) ketones and blood sugar is stabilizing. Concentration was better today, but still not back to normal. Hunger was more noticeable in the morning and afternoon but again, not distressing. Would it have been nice to eat something? Yes, but it didn’t preoccupy my mind. By late evening, hunger is stronger, there is a very mild headache, slight lightheadedness, and stomach growling—this may represent blood sugar falling?—but I was productive late into the evening. I am motivated to keep going by 1) intellectual curiosity and 2) hope that once the ketones are nice and high and the blood glucose is nice and low, hunger will disappear and I’ll feel great. We shall see! I sure am saving a lot of time and money this week…

How much longer did my fasting jump-start to ketosis last? What happened on Day 4 took me completely by surprise! Read about days 4-7 in the next post in this series “Keto for Cancer: Week 1—My Transition to Ketosis.” If you are interested in starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

Dr. Seyfried’s book, Cancer as a Metabolic Disease, inspired me to attempt a fasting jump-start to ketosis to see how long it takes to achieve his “zone of metabolic management.” Read on to see how it’s going so far! (I’m still alive . . . )

Note: this post was originally published on Aug 1, 2013. It was edited to streamline content and improve graphics in June 2016; therefore some older comments may pertain to content that was removed during revision.

Dr. Seyfried’s ketogenic diet for cancer

Caution: dietary experiments with fasting and ketosis are best done under medical supervision, particularly if you have a medical condition or take any daily medications. Everyone’s metabolism is different, so results will vary. Please see my post “Is the Ketogenic Diet Safe for Everyone?“

After reading Dr. Seyfried’s book,1 I immediately felt sympathy for those of you out there who have cancer now, or who are cancer survivors worried about recurrence—were you hoping for a simple nutritional strategy, such as “eat more broccoli” or “add chia seeds to your morning smoothie?” Had I led you down a road of hope and then left you feeling disheartened when you saw how difficult Dr. Seyfried’s diet appeared to be? Let me try to make it up to you by trying his diet myself while you watch from the comfort of your living room.

Seyfried’s fasting jump-start to ketosis

Dr. Seyfried says the fastest way to achieve optimal blood glucose and ketone levels is to begin with a water-only fasting jump-start to ketosis for 3-5 days. Then embark on a low-calorie “ketogenic” diet, aiming for blood sugar levels of 55-65 mg/dL and blood ketone levels of at least 4.0 mM (see article 3 of my cancer series for more details). As a reminder, average blood glucose levels for most healthy people eating a standard diet run between about 70 and 95 mg/dl, and blood ketone levels are usually 0.3 mM or less.

His plan sounded extreme even to me. However, fasting is supposed to be rather comfortable once you get used to it, and ketogenic diets are known for reducing appetite and improving people’s sense of well-being in most cases. Thankfully I do not have cancer, but nevertheless, in an attempt to rekindle the hope that some of you may have lost, I thought I’d take one for the team and try his recommendations myself.

Goals of this experiment

• To see if I can reach Dr. Seyfried’s “zone of metabolic management.”
• To see if I can maintain high ketone levels and low blood sugar levels using my mostly-meat diet [standard ketogenic diets tend to rely heavily on high-fat dairy products, eggs, and coconut oil, none of which I tolerate well].
• To explore the impact of protein: fat ratios, calories, and exercise on ketone and blood sugar levels.
• To compare urine ketones to blood ketones and see if there is any correlation.
• To document effect of this diet on mood, energy, concentration, weight, sleep, etc.
• To document any side effects of this diet.

My N=1 experiment, phase I: fasting jump-start to ketosis

“N=1” refers to an experiment with only one subject (in this case, me). Everyone’s metabolism is different, so please take my experience with a big grain o’ salt. Please note that, just because Dr. Seyfried suggests that a water-only fast is the fastest way to get into ketosis does not mean that it is required. I also can’t say whether faster is necessarily better for your health or easier than a gradual transition to ketosis.

Supplies:

Note on the ketone meter: When I conducted this experiment, the most affordable, accurate ketone meter was the Precision Xtra®. Unfortunately the “affordable” ketone strips cost $2.22 each! I have since found a meter just as accurate, with an array of great features—and the strips are a much more reasonable 99 cents. You can read more about why I recommend the Keto-Mojo glucose/ketone meter on my ketogenic diet and mental health resources page. Because I like their meter and their mission, I’ve partnered with them to offer my readers 15% off of the purchase of any new meter kit. Just click the link here; no coupon code necessary.

Day 1 (1/31/13)

Notes: Much easier day than I had expected. Stomach a little growly, slightly lightheaded, minor difficulty concentrating, vision slightly blurry, low energy. Slept well, but had a funny dream about a granola bar—something I haven’t eaten in nearly six years! Since exercise confuses things, none for now.

Day 2 (2/1/13)

Notes: Fascinating that blood sugar this morning was higher than last night, without any food. This may be due to cortisol and adrenaline reactions to falling blood sugar—these hormones kick in when blood sugar falls to pull it back up again. Mild headache in the morning. More difficulty concentrating today—”spacey” would be the right word—but it only affected my efficiency in doing paperwork. I was otherwise fine and able to work a full day, run errands, drive, etc. Sleep was terrible—slept from 10pm to 1:30 am, then wide awake until 5am, then back to sleep until about 7:30 am. Sleep quality itself was very light and dream-filled, but no granola bar visions tonight. I can’t believe how much easier this is than I thought it would be—I’m not experiencing distressing levels of hunger or cravings.

Day 3 (2/2/13—Happy Groundhog’s Day!)

Notes: Finally, we have the appearance of (modest) ketones and blood sugar is stabilizing. Concentration was better today, but still not back to normal. Hunger was more noticeable in the morning and afternoon but again, not distressing. Would it have been nice to eat something? Yes, but it didn’t preoccupy my mind. By late evening, hunger is stronger, there is a very mild headache, slight lightheadedness, and stomach growling—this may represent blood sugar falling?—but I was productive late into the evening. I am motivated to keep going by 1) intellectual curiosity and 2) hope that once the ketones are nice and high and the blood glucose is nice and low, hunger will disappear and I’ll feel great. We shall see! I sure am saving a lot of time and money this week…

How much longer did my fasting jump-start to ketosis last? What happened on Day 4 took me completely by surprise! Read about days 4-7 in the next post in this series “Keto for Cancer: Week 1—My Transition to Ketosis.” If you are interested in starting a ketogenic diet yourself, see my online guide: “Ketogenic Diets 101.”

The future of cancer prevention and treatment may not be in sexy, high-tech, gene-targeting therapies, but in our own hands . . . or rather, on our own plates. Which diets work best for cancer treatment and prevention?

[This is the 4th in a 4-part article inspired by Dr. Thomas Seyfried’s book Cancer as a Metabolic Disease. Go to “What Causes Cancer? Part I” to begin with the first article.]

Cancer treatments: Standard therapies vs. dietary therapies

Standard therapies

• Conventional treatments can help in the short-term but can cause problems in the long-term.
• Chemotherapy is toxic to healthy cells and can breed resistance among cancer cells, increasing the risk of more aggressive cancers if relapse occurs.
• Radiation turns up the activity of the tumor growth pathway (PI3K/Akt/HIF), which promotes not only tumor growth, but also recruitment of new blood vessels (angiogenesis) and drug resistance.
• Radiation increases fusion activity between cells, which means that normal and healthy cells can merge into hybrid cells and become more aggressive.
• Radiation directly damages mitochondria, which increases risk for cancer in the future.
• Both radiation and immunosuppression therapy (drugs that suppress the immune system) can increase the incidence of metastatic cancers (cancers that spread).
• Steroids such as dexamethasone (Decadron), often used to reduce inflammation, raise blood sugar levels, feeding tumor cells and enhancing their survival.

Dietary therapies

• DER (dietary energy restriction) triggers cancer cell death via apoptosis(programmed cell suicide), which is a natural, noninflammatory process that happens from within the cell, causing no collateral damage. Conventional treatments kill cancer cells via necrosis, an inflammatory process that happens from the outside and is locally destructive. Tumor cells that are being fed glucose/glutamine are resistant to apoptosis, but under ketogenic conditions, they become better able to undergo apoptosis again.
• DER and chemotherapy can both cause weight loss. However, the weight loss associated with DER is healthy and does not weaken people, whereas chemotherapy-induced weight loss is unhealthy and weakens people.

Dr. Seyfried wonders if some of the benefit that some people obtain from chemotherapy may be due to the calorie restriction that occurs due to loss of appetite. He notes that drug studies don’t usually take this possibility into consideration.

“DER (dietary energy restriction) can be considered a broad-spectrum, nontoxic metabolic therapy that inhibits multiple signaling pathways required for progression of malignant tumors regardless of tissue of origin. It is not clear to me why so many oncologists have difficulty appreciating this concept.

“Therapies that reduce glucose and elevate ketones can starve glucose-dependent cancer cells while protecting and fueling healthy cells. There is no other cancer therapy that can do this.”

Complementary cancer-fighting strategies

Dr. Seyfried does not think that dietary restriction alone is sufficient to fight most cancers, so he proposes some additional strategies that can be used in combination with dietary measures to optimize results:

• “Anti-glycolytic” drugs that reduce the activity of the glycolysis (fermentation) pathway, which is the primary energy pathway for most cancer cells.

“Anti-glycolytic drugs together with energy-restricted diets could act as a powerful double ‘metabolic punch’ for the rapid killing of glycolysis-dependent tumor cells.”

• “CR-mimetic” drugs that mimic the effects of calorie restriction by lowering glucose levels. These drugs should not be used without diet, because they lower glucose without raising ketones. Without ketones, healthy cells could die of energy failure—they would have neither glucose nor ketones for fuel.
• Hyperbaric (high pressure, 100%) oxygen. Excess oxygen reduces the activity of an enzyme called hexokinase II, which grabs onto glucose after it enters cells and traps it inside so it can be burned for energy.

But standard treatment sometimes works and diet doesn’t always work . . .

We all know people who have undergone successful standard treatments and who have not had a recurrence of cancer. My own mother had cancer twice, decades ago, and has had no cancer since. In both cases surgery was curative for her. If you are lucky enough to have a simple form of cancer in a body part that can be completely removed, and you catch it before it spreads, your prognosis is probably pretty good.

Chemotherapy and radiation can kill many cancer cells because (as discussed in article #1), they are more vulnerable to these agents than healthy cells, and if you have a healthy enough immune system, your own body may be able to take care of the rest. Some people never get cancer again—they may change their lifestyle after a cancer scare and start taking better care of themselves (my mother stopped smoking, for example). Some adopt a healthier diet or start exercising. Some may just be lucky. But clearly modern cancer therapies have made a difference for some people, including my own mother.

So my mom is a cancer success story, but a close family friend of ours who was diagnosed with glioblastoma multiforme (brain cancer) was not so lucky. She lived for only a few months, and those final months were of very poor quality. She had smoked for years, but had quit long before her diagnosis. She loved candy. As kids we always looked forward to her visits, because she always walked through the door with a big package of red licorice and a king-sized bag of m&m’s. And as soon as she ran out of treats, she’d say to my mother: “Ain’tcha got somethin’ sweet?”

I have no idea why she got brain cancer, of course, but modern treatments certainly were not able to help her. I do find it interesting that the second most common type of cancer among young people is brain cancer, and the brain just happens to be the organ most heavily dependent on glucose. Could it be that the brain is especially sensitive to the damaging effects of high sugar/high flour diets?

Ketogenic diet for cancer case studies

First study of ketogenic diet with human brain malignancy

Linda Nebeling, PhD, MPH, RD (now with the National Cancer Institute) authored the first-ever study of a ketogenic diet in human brain malignancy [Nebeling 1995]. This was a landmark study of two young girls with advanced-stage, inoperable brain tumors that had not responded to traditional therapies. A three-year-old girl with stage IV astrocytoma and an eight year old girl with grade III astrocytoma were treated with a ketogenic diet. Both children responded well, and experienced long-term tumor management without further chemotherapy or radiation. PET scans revealed a 22% reduction in glucose uptake by tumors in both girls.

Low-calorie/ketogenic diet with brain tumors

Giulio Zuccoli MD (Italian neuro-radiologist) and Thomas Seyfried PhD published a case report [Zuccoli 2010] of a middle-aged woman with glioblastoma (a form of brain cancer) who was treated with a 600-calorie/day ketogenic diet. Upon diagnosis, steroids (to control inflammation) and anticonvulsant medication (to control seizures) were given. She underwent surgery, fasted briefly, and then began the diet. After 14 days on the diet, steroids were stopped, and chemotherapy and radiation treatments were started. After two months, chemotherapy and radiation were discontinued. One week later, PET scan and MRI were performed and no tumor tissue or swelling was detected.The patient stopped the diet, and 10 weeks later, MRI showed evidence that the tumor had come back.

This case report demonstrated that a) the ketogenic diet was well-tolerated; b) the diet may be a useful add-on therapy, as most tumors of her type do not respond as well as hers did to standard treatments alone, and c) inflammation was well-controlled without the usual need for steroids, supporting the anti-inflammatory properties of the diet.

Very low-carb diet in ten patients with incurable cancers

Eugene Fine, MD, professor of nuclear medicine at Albert Einstein College of Medicine just published a 28-day pilot study [Fine 2012] of a very low carbohydrate diet in ten men and women ages 53-73 with incurable, advanced cancers of a variety of types (3 colon, 2 breast, 2 lung, 1 ovarian, 1 esophageal, 1 fallopian tube). Carbohydrate intake was about 9%, but protein and fat were not restricted. Interestingly, those with high ketone levels (and low insulin levels) were the only ones whose tumors either stopped growing or got smaller as evidenced by PET scan. His video presentation is below in the resources section. Dr. Fine’s study is groundbreaking because it may pave the way for additional studies, which are badly needed. Below is his video presentation from the 2012 Ancestral Health Symposium entitled: “Dietary Insulin Inhibition as a Metabolic Therapy in Advanced Cancer.”

Ketogenic diet in four patients with brain cancer

Beth Zupec-Kania, RD is a nutritionist with the Charlie Foundation (an organization dedicated to raising awareness of and providing support for the use of ketogenic diets in children with epilepsy). Ten glioma (brain cancer) patients contacted her for help in using ketogenic diets in the treatment of their cancer. Four of them ultimately committed to a strictly supervised ketogenic diet. Three of the four patients had stable or atrophied (reduced) tumor size documented by MRI. Two had been on the diet for several years and were still alive despite having initially been given only a few months to live. One patient died; he had had advanced stage metastatic cancer prior to starting the ketogenic diet. He remained active and alert until the last two months of his life, and outlived his prognosis by a year.

Obstacles to dietary treatments

Ketogenic diets are hard to follow. They require careful monitoring, tremendous self-discipline, and essentially require that people turn their usual diet completely upside-down. You’ve got to be very motivated, and have the full support of everyone who lives with you. Even if everyone on the planet were 100% convinced that a ketogenic diet is the best diet for cancer, I would eat my hat if everyone with cancer followed it. That would be unrealistic—changing one’s diet is hard.

Ketogenic diets are, by nature, high-fat diets, and this will bother some people on a psychological level, due to (unnecessary) fear of eating fat. For more information, see my fats page and my cholesterol page.

Most physicians are taught next to nothing about nutrition during medical training, and once in practice, are too busy to learn. Nutritional treatments are not particularly sexy or high-tech and may not be of interest to some physicians. Nutritional treatments may be viewed as slower to take effect, and as time-consuming to implement.

But here is the most important obstacle: if a particular treatment is not sanctioned by the medical establishment and does not have solid studies behind it, most doctors will be afraid to recommend it or even support it, due to discomfort with uncertainty and fears of medical malpractice. Doctors take their responsibilities very seriously and want to provide the best treatment they can. In today’s world, that means applying the “standard of care.” Currently surgery, chemotherapy, and radiation are the standard of care. And what’s more, is that the standard of care is what insurance companies will pay for. They are unlikely to cover ketone meters, testing strips, special nutritional counseling, etc.

Is your doctor simply keeping up with the standard of care or is he or she interested in being on the cutting edge? Would your doctor be willing to read Dr. Seyfried’s book, or at least his journal article? [see references below]

The good news is you do not need your doctor’s permission to eat a ketogenic diet, only his or her support and willingness to monitor your progress. Open-minded, patient-centered physicians should be on board with your efforts so long as you are willing to take responsibility for your care.

Do ketogenic diets really need to be so strict?

If you read article 3, you may have been disheartened to see how tough Dr. Seyfried’s dietary recommendations are. Yet as draconian as his diet is, he doesn’t think it will work very well on its own without chemotherapy. While no treatments of any kind are perfect, if Dr. Seyfried’s hypothesis about mitochondria and diet are correct, shouldn’t they have the potential to work better than he thinks they will?

Having read his book and heard him speak, I believe Dr. Seyfried is a brilliant scientist and thinker. The only (gentle, constructive, but wicked important) criticism I have is the same one I have of most scientists who study diet—he thinks about diet as a simple collection of proteins, carbohydrates, and fats, and neglects the actual foods in the diet.

Dr. Seyfried compared two different types of chow in mice with cancer—one high-carb “standard” chow and one high fat “ketogenic” chow. He found that the ketogenic chow did not work against cancer if you let the mice eat as much as they wanted. Their little blood sugar levels stayed high and their cancers grew. He had to lower their calories to see benefits. He concluded that both diets worked equally well as long as you lowered calories—a lot. This made me suspicious, so I visited the chow manufacturers’ websites to see what the diets actually contained. I wonder if it will shock you as much as it shocked me.

Dr. Seyfried’s standard high-carb chow:

ProLab RMH 3000 (LabDiet)—62% carbohydrate, 22% protein, 5% fat, 5% fiber

Ingredients: ground wheat, dehulled soybean meal, wheat middlings, ground corn, fish meal, pork fat, alfalfa meal, calcium carbonate, brewer’s yeast, soybean oil, salt, vitamins, and minerals.

The first four ingredients are refined grains and legumes. Nearly 100% refined junk (including lots of refined carbohydrate) that no self-respecting mouse would naturally consume. No wonder he had to limit how much of this stuff the mice ate by 30-60% in order to lower blood glucose.

Dr. Seyfried’s ketogenic chow:

Ketocal (Nutricia)—90% fat, 1.6% carbohydrate, 8.4% protein

Ingredients: hydrogenated soybean oil, dry whole milk, refined soybean oil, soy lecithin, corn syrup solids.

Nice. Processed soy, dairy, and corn syrup. Poor little mice.

If you have read my dairy page, you will know that the whey proteins in milk raise insulin levels, which can prevent ketosis. This may have been why he had to limit how much of this stuff the mice ate to get good results.

To Dr. Seyfried’s credit, he points out in his book that other researchers have been able to achieve good results in their animal cancer experiments without having to restrict calories and he is unable to explain why. Let’s look at a mouse diet that worked without restricting calories:

Unrestricted ketogenic chow:

Ketogenic Bio-Serv F3666—8.36% protein, 0.76% carbohydrates and 78.8% fat

Ingredients: lard, butter, corn oil, casein, cellulose, mineral mix, vitamin mix, dextrose

Look, ma, no whey protein and no refined carbohydrate! The mice could eat as much of this (admittedly very weird) chow and get good results [Stafford 2010]. It makes me hopeful that even this odd diet, which is a far cry from a healthy mouse diet, delivered positive results.

Dr. Seyfried also referred to another study that used a high-protein, low-carb diet with unrestricted calories that also worked, but I could not locate the article in time to include it here. [Ho 2011]

I can’t help but wonder how these little mice would have fared had they been fed real food that mice are actually supposed to be eating.

So, do we need to restrict calories or not? It may depend on the composition of the diet . . . I think the jury is still out. However, people who eat well-formulated ketogenic diets report a substantial reduction in appetite and tend to naturally find themselves eating quite a bit less without having to count calories.

Metastatic cancer is different

Ninety percent of all cancer deaths are due to metastatic disease (cancer that has spread to more than one organ). These are the bad boys. Once cancer is on the move it’s very hard to stop, which is why prevention is so important. But before we get to that, one of the most fascinating topics in Dr. Seyfried’s book is his theory of how and why some cancers travel through the body to distant organs. He makes a compelling argument for the role of a particular kind of immune cell called a macrophage in helping cancers to spread.

The normal role of macrophages (macs) in our immune system is a very complicated and special one. These are amazing cells, with the ability to change their personality, shape, and behavior whenever necessary, depending on the local circumstances. Every macrophage begins its little life as monocyte, a round cell that can cruise the bloodstream. When trouble is lurking anywhere in the body—if there is injury or inflammation or infection—monocytes heed the call of damaged tissues and travel to the troubled area. Once they are close enough, they squeeze themselves out of the blood vessel and into local tissue, where they magically morph into macrophages so they can to get to work.

Macrophages assess the situation and release all kinds of special chemical signals to help recruit other types of immune cells to the scene. But the coolest thing about macrophages is that they can swallow stuff whole. MAC ATTACK!! Macs engulf our own used-up, damaged, or dead cells, and devour bacteria that can do us harm.

When macs run amok . . .

Now these cells are our best friends in infection or wound healing, but if they become cancerous, they can become our worst enemy, because they are very active, can fuse with other cells, and they are mobile. Now you’ve got macs gone amok. Metastatic tumor cells of many types have been observed to have phagocytic behavior (i.e. they eat other cells…just like macs do). Macs are often found mixed in among tumor cells, contributing to chronic inflammation in the area by triggering local immune reactions. These macs are called TAM’s, or tumor-associated macrophages. Tumors containing TAM’s have a poorer prognosis.

Macs tend to hang out more often in their favorite organs—they are especially drawn to lung, liver, and bone. These also happen to be favorite places for cancer to migrate to, as well. Some cancers also like to spread to injured or inflamed parts of the body, just like a mac would. Plants and certain lower animals, which do not have macrophages, can also get cancer, but their cancers never metastasize. Fascinating.

How best to prevent cancer in the first place?

Since 90% of all cancer deaths are due to metastatic cancers (cancers that have spread to more than one organ)—and this estimate has not changed in 50 years—early detection and prevention of spread plays a MAJOR role in prognosis. But the good news is that most cancer IS preventable.

About 5% of cancers are caused by mutations that are inherited at birth. About 15% of cancers are caused by viruses. The rest—a full 80%—are associated with the following risk factors:

• Smoking
• Alcohol
• Obesity
• Age
• Radiation exposure
• Carcinogenic chemical exposure

This means that the vast majority of cancers are preventable using lifestyle modifications. Dr. Seyfried writes (and I have read many papers supporting this logic), that the best way to prevent cancer (and most chronic diseases, for that matter), is to avoid exposure to things that cause tissue inflammation. All of the above risk factors are directly associated with inflammation. Two of the above risk factors are dietary—alcohol and obesity, so let’s zero in on those. This is a nutrition website, after all.

What is the connection between obesity and inflammation?

The road to inflammation is paved with refined carbohydrates. To fully explain the science behind these connections here would take us too far off track, but suffice it to say for now that refined carbohydrates (such as sugar and flour) lead to high blood sugar and high insulin levels. These, in turn, increase the production of damaging free radicals within the mitochondria. They also increase the production of a molecule called NF-kappa-B, which turns on genes that promote inflammation. It would therefore make sense, whether you are overweight or not, to minimize your exposure to refined carbohydrates.

Obesity is a major risk factor for cancer, and there is no question that diet is the most powerful tool available to manage weight. If you have been paying attention to thought leaders in the field of obesity, or you are familiar with the information on this website about obesity, or you have learned through your own experiences what works best, you know that the single most effective dietary strategy for preventing and managing weight gain (as well as for preventing and managing most chronic diseases of civilization) is avoiding refined carbohydrates. Refined carbohydrates keep blood sugar and insulin levels high, promoting inflammation and oxidation throughout the body. They also encourage overeating due to loss of control over appetite, which continues the vicious cycle.

Yet we all know people with cancer who are not overweight and who seem to take excellent care of themselves. We even know of athletes who don’t drink, don’t smoke, and are in excellent physical condition, who nevertheless have come down with cancer. Could it be that refined carbohydrate is the hidden risk factor in people like this? To learn more about the connection between carbohydrates and cancer, there is an excellent review article available free on line.

In addition to avoiding inflammation, Dr. Seyfried recommends a 7-day, water-only fast once a year. His reasoning is that a total fast forces the body to rid itself of damaged and weakened cells that may be pre-cancerous. With nothing else to eat, healthy cells turn to cannibalism, eating their vulnerable neighboring cells. How’s that for an image?

The bottom line

The bottom line is that diet clearly makes a huge difference, but we don’t yet know what the ideal diet for cancer treatment is. There is no question in my mind at this point that carbohydrates are bad for cancer. To what degree calories, protein and fat need to be restricted is unclear. We need more studies, and they need to be more thoughtfully designed. It seems that ketogenic diets have tremendous potential, but I don’t know if they need to be as strict as Dr. Seyfried recommends. Might people who design their ketogenic diet around healthy, whole foods and avoid dairy be able to get away with more calories?

I do think it makes sense for those of us who want to reduce our risk for cancer to minimize refined carbohydrates, minimize dairy products (particularly those with high whey content), maintain our weight in a healthy range, and choose whole foods over processed foods. Since that dietary pattern is already quite an improvement from the standard American diet, I have hope that it could make a big difference in our risk for cancer (as well as many chronic diseases).

However, if I already had cancer or were a cancer survivor, I wouldn’t touch a carbohydrate with a 10-foot pole. Dairy, being a growth formula (for baby cows), would also be off the menu.

Taking one for the team

Dr. Seyfried’s book, Cancer as a Metabolic Disease,inspired me to attempt a fasting jump-start to ketosis to see how long it takes to achieve his “zone of metabolic management.” To read about my 5-week experiment with Dr. Seyfried’s dietary recommendations, start with the first post: Seyfried’s Cancer Diet: My Fasting Jump-Start to Ketosis.

The future of cancer prevention and treatment may not be in sexy, high-tech, gene-targeting therapies, but in our own hands . . . or rather, on our own plates. Which diets work best for cancer treatment and prevention?

[This is the 4th in a 4-part article inspired by Dr. Thomas Seyfried’s book Cancer as a Metabolic Disease. Go to “What Causes Cancer? Part I” to begin with the first article.]

Cancer treatments: Standard therapies vs. dietary therapies

Standard therapies

• Conventional treatments can help in the short-term but can cause problems in the long-term.
• Chemotherapy is toxic to healthy cells and can breed resistance among cancer cells, increasing the risk of more aggressive cancers if relapse occurs.
• Radiation turns up the activity of the tumor growth pathway (PI3K/Akt/HIF), which promotes not only tumor growth, but also recruitment of new blood vessels (angiogenesis) and drug resistance.
• Radiation increases fusion activity between cells, which means that normal and healthy cells can merge into hybrid cells and become more aggressive.
• Radiation directly damages mitochondria, which increases risk for cancer in the future.
• Both radiation and immunosuppression therapy (drugs that suppress the immune system) can increase the incidence of metastatic cancers (cancers that spread).
• Steroids such as dexamethasone (Decadron), often used to reduce inflammation, raise blood sugar levels, feeding tumor cells and enhancing their survival.

Dietary therapies

• DER (dietary energy restriction) triggers cancer cell death via apoptosis(programmed cell suicide), which is a natural, noninflammatory process that happens from within the cell, causing no collateral damage. Conventional treatments kill cancer cells via necrosis, an inflammatory process that happens from the outside and is locally destructive. Tumor cells that are being fed glucose/glutamine are resistant to apoptosis, but under ketogenic conditions, they become better able to undergo apoptosis again.
• DER and chemotherapy can both cause weight loss. However, the weight loss associated with DER is healthy and does not weaken people, whereas chemotherapy-induced weight loss is unhealthy and weakens people.

Dr. Seyfried wonders if some of the benefit that some people obtain from chemotherapy may be due to the calorie restriction that occurs due to loss of appetite. He notes that drug studies don’t usually take this possibility into consideration.

“DER (dietary energy restriction) can be considered a broad-spectrum, nontoxic metabolic therapy that inhibits multiple signaling pathways required for progression of malignant tumors regardless of tissue of origin. It is not clear to me why so many oncologists have difficulty appreciating this concept.

“Therapies that reduce glucose and elevate ketones can starve glucose-dependent cancer cells while protecting and fueling healthy cells. There is no other cancer therapy that can do this.”

Complementary cancer-fighting strategies

Dr. Seyfried does not think that dietary restriction alone is sufficient to fight most cancers, so he proposes some additional strategies that can be used in combination with dietary measures to optimize results:

• “Anti-glycolytic” drugs that reduce the activity of the glycolysis (fermentation) pathway, which is the primary energy pathway for most cancer cells.

“Anti-glycolytic drugs together with energy-restricted diets could act as a powerful double ‘metabolic punch’ for the rapid killing of glycolysis-dependent tumor cells.”

• “CR-mimetic” drugs that mimic the effects of calorie restriction by lowering glucose levels. These drugs should not be used without diet, because they lower glucose without raising ketones. Without ketones, healthy cells could die of energy failure—they would have neither glucose nor ketones for fuel.
• Hyperbaric (high pressure, 100%) oxygen. Excess oxygen reduces the activity of an enzyme called hexokinase II, which grabs onto glucose after it enters cells and traps it inside so it can be burned for energy.

But standard treatment sometimes works and diet doesn’t always work . . .

We all know people who have undergone successful standard treatments and who have not had a recurrence of cancer. My own mother had cancer twice, decades ago, and has had no cancer since. In both cases surgery was curative for her. If you are lucky enough to have a simple form of cancer in a body part that can be completely removed, and you catch it before it spreads, your prognosis is probably pretty good.

Chemotherapy and radiation can kill many cancer cells because (as discussed in article #1), they are more vulnerable to these agents than healthy cells, and if you have a healthy enough immune system, your own body may be able to take care of the rest. Some people never get cancer again—they may change their lifestyle after a cancer scare and start taking better care of themselves (my mother stopped smoking, for example). Some adopt a healthier diet or start exercising. Some may just be lucky. But clearly modern cancer therapies have made a difference for some people, including my own mother.

So my mom is a cancer success story, but a close family friend of ours who was diagnosed with glioblastoma multiforme (brain cancer) was not so lucky. She lived for only a few months, and those final months were of very poor quality. She had smoked for years, but had quit long before her diagnosis. She loved candy. As kids we always looked forward to her visits, because she always walked through the door with a big package of red licorice and a king-sized bag of m&m’s. And as soon as she ran out of treats, she’d say to my mother: “Ain’tcha got somethin’ sweet?”

I have no idea why she got brain cancer, of course, but modern treatments certainly were not able to help her. I do find it interesting that the second most common type of cancer among young people is brain cancer, and the brain just happens to be the organ most heavily dependent on glucose. Could it be that the brain is especially sensitive to the damaging effects of high sugar/high flour diets?

Ketogenic diet for cancer case studies

First study of ketogenic diet with human brain malignancy

Linda Nebeling, PhD, MPH, RD (now with the National Cancer Institute) authored the first-ever study of a ketogenic diet in human brain malignancy [Nebeling 1995]. This was a landmark study of two young girls with advanced-stage, inoperable brain tumors that had not responded to traditional therapies. A three-year-old girl with stage IV astrocytoma and an eight year old girl with grade III astrocytoma were treated with a ketogenic diet. Both children responded well, and experienced long-term tumor management without further chemotherapy or radiation. PET scans revealed a 22% reduction in glucose uptake by tumors in both girls.

Low-calorie/ketogenic diet with brain tumors

Giulio Zuccoli MD (Italian neuro-radiologist) and Thomas Seyfried PhD published a case report [Zuccoli 2010] of a middle-aged woman with glioblastoma (a form of brain cancer) who was treated with a 600-calorie/day ketogenic diet. Upon diagnosis, steroids (to control inflammation) and anticonvulsant medication (to control seizures) were given. She underwent surgery, fasted briefly, and then began the diet. After 14 days on the diet, steroids were stopped, and chemotherapy and radiation treatments were started. After two months, chemotherapy and radiation were discontinued. One week later, PET scan and MRI were performed and no tumor tissue or swelling was detected.The patient stopped the diet, and 10 weeks later, MRI showed evidence that the tumor had come back.

This case report demonstrated that a) the ketogenic diet was well-tolerated; b) the diet may be a useful add-on therapy, as most tumors of her type do not respond as well as hers did to standard treatments alone, and c) inflammation was well-controlled without the usual need for steroids, supporting the anti-inflammatory properties of the diet.

Very low-carb diet in ten patients with incurable cancers

Eugene Fine, MD, professor of nuclear medicine at Albert Einstein College of Medicine just published a 28-day pilot study [Fine 2012] of a very low carbohydrate diet in ten men and women ages 53-73 with incurable, advanced cancers of a variety of types (3 colon, 2 breast, 2 lung, 1 ovarian, 1 esophageal, 1 fallopian tube). Carbohydrate intake was about 9%, but protein and fat were not restricted. Interestingly, those with high ketone levels (and low insulin levels) were the only ones whose tumors either stopped growing or got smaller as evidenced by PET scan. His video presentation is below in the resources section. Dr. Fine’s study is groundbreaking because it may pave the way for additional studies, which are badly needed. Below is his video presentation from the 2012 Ancestral Health Symposium entitled: “Dietary Insulin Inhibition as a Metabolic Therapy in Advanced Cancer.”

Ketogenic diet in four patients with brain cancer

Beth Zupec-Kania, RD is a nutritionist with the Charlie Foundation (an organization dedicated to raising awareness of and providing support for the use of ketogenic diets in children with epilepsy). Ten glioma (brain cancer) patients contacted her for help in using ketogenic diets in the treatment of their cancer. Four of them ultimately committed to a strictly supervised ketogenic diet. Three of the four patients had stable or atrophied (reduced) tumor size documented by MRI. Two had been on the diet for several years and were still alive despite having initially been given only a few months to live. One patient died; he had had advanced stage metastatic cancer prior to starting the ketogenic diet. He remained active and alert until the last two months of his life, and outlived his prognosis by a year.

Obstacles to dietary treatments

Ketogenic diets are hard to follow. They require careful monitoring, tremendous self-discipline, and essentially require that people turn their usual diet completely upside-down. You’ve got to be very motivated, and have the full support of everyone who lives with you. Even if everyone on the planet were 100% convinced that a ketogenic diet is the best diet for cancer, I would eat my hat if everyone with cancer followed it. That would be unrealistic—changing one’s diet is hard.

Ketogenic diets are, by nature, high-fat diets, and this will bother some people on a psychological level, due to (unnecessary) fear of eating fat. For more information, see my fats page and my cholesterol page.

Most physicians are taught next to nothing about nutrition during medical training, and once in practice, are too busy to learn. Nutritional treatments are not particularly sexy or high-tech and may not be of interest to some physicians. Nutritional treatments may be viewed as slower to take effect, and as time-consuming to implement.

But here is the most important obstacle: if a particular treatment is not sanctioned by the medical establishment and does not have solid studies behind it, most doctors will be afraid to recommend it or even support it, due to discomfort with uncertainty and fears of medical malpractice. Doctors take their responsibilities very seriously and want to provide the best treatment they can. In today’s world, that means applying the “standard of care.” Currently surgery, chemotherapy, and radiation are the standard of care. And what’s more, is that the standard of care is what insurance companies will pay for. They are unlikely to cover ketone meters, testing strips, special nutritional counseling, etc.

Is your doctor simply keeping up with the standard of care or is he or she interested in being on the cutting edge? Would your doctor be willing to read Dr. Seyfried’s book, or at least his journal article? [see references below]

The good news is you do not need your doctor’s permission to eat a ketogenic diet, only his or her support and willingness to monitor your progress. Open-minded, patient-centered physicians should be on board with your efforts so long as you are willing to take responsibility for your care.

Do ketogenic diets really need to be so strict?

If you read article 3, you may have been disheartened to see how tough Dr. Seyfried’s dietary recommendations are. Yet as draconian as his diet is, he doesn’t think it will work very well on its own without chemotherapy. While no treatments of any kind are perfect, if Dr. Seyfried’s hypothesis about mitochondria and diet are correct, shouldn’t they have the potential to work better than he thinks they will?

Having read his book and heard him speak, I believe Dr. Seyfried is a brilliant scientist and thinker. The only (gentle, constructive, but wicked important) criticism I have is the same one I have of most scientists who study diet—he thinks about diet as a simple collection of proteins, carbohydrates, and fats, and neglects the actual foods in the diet.

Dr. Seyfried compared two different types of chow in mice with cancer—one high-carb “standard” chow and one high fat “ketogenic” chow. He found that the ketogenic chow did not work against cancer if you let the mice eat as much as they wanted. Their little blood sugar levels stayed high and their cancers grew. He had to lower their calories to see benefits. He concluded that both diets worked equally well as long as you lowered calories—a lot. This made me suspicious, so I visited the chow manufacturers’ websites to see what the diets actually contained. I wonder if it will shock you as much as it shocked me.

Dr. Seyfried’s standard high-carb chow:

ProLab RMH 3000 (LabDiet)—62% carbohydrate, 22% protein, 5% fat, 5% fiber

Ingredients: ground wheat, dehulled soybean meal, wheat middlings, ground corn, fish meal, pork fat, alfalfa meal, calcium carbonate, brewer’s yeast, soybean oil, salt, vitamins, and minerals.

The first four ingredients are refined grains and legumes. Nearly 100% refined junk (including lots of refined carbohydrate) that no self-respecting mouse would naturally consume. No wonder he had to limit how much of this stuff the mice ate by 30-60% in order to lower blood glucose.

Dr. Seyfried’s ketogenic chow:

Ketocal (Nutricia)—90% fat, 1.6% carbohydrate, 8.4% protein

Ingredients: hydrogenated soybean oil, dry whole milk, refined soybean oil, soy lecithin, corn syrup solids.

Nice. Processed soy, dairy, and corn syrup. Poor little mice.

If you have read my dairy page, you will know that the whey proteins in milk raise insulin levels, which can prevent ketosis. This may have been why he had to limit how much of this stuff the mice ate to get good results.

To Dr. Seyfried’s credit, he points out in his book that other researchers have been able to achieve good results in their animal cancer experiments without having to restrict calories and he is unable to explain why. Let’s look at a mouse diet that worked without restricting calories:

Unrestricted ketogenic chow:

Ketogenic Bio-Serv F3666—8.36% protein, 0.76% carbohydrates and 78.8% fat

Ingredients: lard, butter, corn oil, casein, cellulose, mineral mix, vitamin mix, dextrose

Look, ma, no whey protein and no refined carbohydrate! The mice could eat as much of this (admittedly very weird) chow and get good results [Stafford 2010]. It makes me hopeful that even this odd diet, which is a far cry from a healthy mouse diet, delivered positive results.

Dr. Seyfried also referred to another study that used a high-protein, low-carb diet with unrestricted calories that also worked, but I could not locate the article in time to include it here. [Ho 2011]

I can’t help but wonder how these little mice would have fared had they been fed real food that mice are actually supposed to be eating.

So, do we need to restrict calories or not? It may depend on the composition of the diet . . . I think the jury is still out. However, people who eat well-formulated ketogenic diets report a substantial reduction in appetite and tend to naturally find themselves eating quite a bit less without having to count calories.

Metastatic cancer is different

Ninety percent of all cancer deaths are due to metastatic disease (cancer that has spread to more than one organ). These are the bad boys. Once cancer is on the move it’s very hard to stop, which is why prevention is so important. But before we get to that, one of the most fascinating topics in Dr. Seyfried’s book is his theory of how and why some cancers travel through the body to distant organs. He makes a compelling argument for the role of a particular kind of immune cell called a macrophage in helping cancers to spread.

The normal role of macrophages (macs) in our immune system is a very complicated and special one. These are amazing cells, with the ability to change their personality, shape, and behavior whenever necessary, depending on the local circumstances. Every macrophage begins its little life as monocyte, a round cell that can cruise the bloodstream. When trouble is lurking anywhere in the body—if there is injury or inflammation or infection—monocytes heed the call of damaged tissues and travel to the troubled area. Once they are close enough, they squeeze themselves out of the blood vessel and into local tissue, where they magically morph into macrophages so they can to get to work.

Macrophages assess the situation and release all kinds of special chemical signals to help recruit other types of immune cells to the scene. But the coolest thing about macrophages is that they can swallow stuff whole. MAC ATTACK!! Macs engulf our own used-up, damaged, or dead cells, and devour bacteria that can do us harm.

When macs run amok . . .

Now these cells are our best friends in infection or wound healing, but if they become cancerous, they can become our worst enemy, because they are very active, can fuse with other cells, and they are mobile. Now you’ve got macs gone amok. Metastatic tumor cells of many types have been observed to have phagocytic behavior (i.e. they eat other cells…just like macs do). Macs are often found mixed in among tumor cells, contributing to chronic inflammation in the area by triggering local immune reactions. These macs are called TAM’s, or tumor-associated macrophages. Tumors containing TAM’s have a poorer prognosis.

Macs tend to hang out more often in their favorite organs—they are especially drawn to lung, liver, and bone. These also happen to be favorite places for cancer to migrate to, as well. Some cancers also like to spread to injured or inflamed parts of the body, just like a mac would. Plants and certain lower animals, which do not have macrophages, can also get cancer, but their cancers never metastasize. Fascinating.

How best to prevent cancer in the first place?

Since 90% of all cancer deaths are due to metastatic cancers (cancers that have spread to more than one organ)—and this estimate has not changed in 50 years—early detection and prevention of spread plays a MAJOR role in prognosis. But the good news is that most cancer IS preventable.

About 5% of cancers are caused by mutations that are inherited at birth. About 15% of cancers are caused by viruses. The rest—a full 80%—are associated with the following risk factors:

• Smoking
• Alcohol
• Obesity
• Age
• Radiation exposure
• Carcinogenic chemical exposure

This means that the vast majority of cancers are preventable using lifestyle modifications. Dr. Seyfried writes (and I have read many papers supporting this logic), that the best way to prevent cancer (and most chronic diseases, for that matter), is to avoid exposure to things that cause tissue inflammation. All of the above risk factors are directly associated with inflammation. Two of the above risk factors are dietary—alcohol and obesity, so let’s zero in on those. This is a nutrition website, after all.

What is the connection between obesity and inflammation?

The road to inflammation is paved with refined carbohydrates. To fully explain the science behind these connections here would take us too far off track, but suffice it to say for now that refined carbohydrates (such as sugar and flour) lead to high blood sugar and high insulin levels. These, in turn, increase the production of damaging free radicals within the mitochondria. They also increase the production of a molecule called NF-kappa-B, which turns on genes that promote inflammation. It would therefore make sense, whether you are overweight or not, to minimize your exposure to refined carbohydrates.

Obesity is a major risk factor for cancer, and there is no question that diet is the most powerful tool available to manage weight. If you have been paying attention to thought leaders in the field of obesity, or you are familiar with the information on this website about obesity, or you have learned through your own experiences what works best, you know that the single most effective dietary strategy for preventing and managing weight gain (as well as for preventing and managing most chronic diseases of civilization) is avoiding refined carbohydrates. Refined carbohydrates keep blood sugar and insulin levels high, promoting inflammation and oxidation throughout the body. They also encourage overeating due to loss of control over appetite, which continues the vicious cycle.

Yet we all know people with cancer who are not overweight and who seem to take excellent care of themselves. We even know of athletes who don’t drink, don’t smoke, and are in excellent physical condition, who nevertheless have come down with cancer. Could it be that refined carbohydrate is the hidden risk factor in people like this? To learn more about the connection between carbohydrates and cancer, there is an excellent review article available free on line.

In addition to avoiding inflammation, Dr. Seyfried recommends a 7-day, water-only fast once a year. His reasoning is that a total fast forces the body to rid itself of damaged and weakened cells that may be pre-cancerous. With nothing else to eat, healthy cells turn to cannibalism, eating their vulnerable neighboring cells. How’s that for an image?

The bottom line

The bottom line is that diet clearly makes a huge difference, but we don’t yet know what the ideal diet for cancer treatment is. There is no question in my mind at this point that carbohydrates are bad for cancer. To what degree calories, protein and fat need to be restricted is unclear. We need more studies, and they need to be more thoughtfully designed. It seems that ketogenic diets have tremendous potential, but I don’t know if they need to be as strict as Dr. Seyfried recommends. Might people who design their ketogenic diet around healthy, whole foods and avoid dairy be able to get away with more calories?

I do think it makes sense for those of us who want to reduce our risk for cancer to minimize refined carbohydrates, minimize dairy products (particularly those with high whey content), maintain our weight in a healthy range, and choose whole foods over processed foods. Since that dietary pattern is already quite an improvement from the standard American diet, I have hope that it could make a big difference in our risk for cancer (as well as many chronic diseases).

However, if I already had cancer or were a cancer survivor, I wouldn’t touch a carbohydrate with a 10-foot pole. Dairy, being a growth formula (for baby cows), would also be off the menu.

Taking one for the team

Dr. Seyfried’s book, Cancer as a Metabolic Disease,inspired me to attempt a fasting jump-start to ketosis to see how long it takes to achieve his “zone of metabolic management.” To read about my 5-week experiment with Dr. Seyfried’s dietary recommendations, start with the first post: Seyfried’s Cancer Diet: My Fasting Jump-Start to Ketosis.

Thomas Seyfried PhD, a brain cancer researcher with over 25 years of experience in the field, gave a groundbreaking presentation about cancer at the Ancestral Health Symposium held at Harvard Law School this past August. The three main take-home points of his talk:

1. Cancer is not caused by genetic mutations
2. Cancer is a mitochondrial disease
3. Cancer can be treated with ketogenic diets

The gene theory of cancer

In case your basic biology is rusty: our genes are made of DNA—coils of coded information that tell our cells exactly how to build all the proteins they need to conduct their daily business. These blueprints have to be flexible, because cells need different proteins under different circumstances. Cells must be able to adapt to various conditions, such as stress, injury, infection, temperature changes, and food supply. So, genes contain lots of special controls that can be turned on and off, depending on what’s going on in and around the cell.

I was taught in medical school that cancer is about genes going haywire—something evil comes along, like a toxic chemical or a beam of radiation, attacks your DNA, and poof—you’ve got cancer (unless you are a cartoon character, in which case you develop superpowers). Mutant cells start dividing like crazy and taking over your body. I was also taught that the way to get rid of cancer is to flood it with toxic chemicals and radiation . . . hmmm . . .

The company line is that cancer is caused by mutations (changes) in DNA that transform healthy, well-behaved cells into reckless, ravenous, immortal renegades. These mutations hijack the set of instructions encoded in the cells’ DNA, and scientists think these mutations cause cells to go wild.

Differences between healthy cells and cancer cells

Cancer cells are very different from normal cells. They grow independently, ignoring the anti-growth signals and death cues that would normally keep healthy cells from getting out of control. Cancer cells create their own blood supply and can divide forever. They lose many of the physical features of their mother cells; they are usually smaller, and may be disfigured or even shapeless. Sometimes they fuse with each other or with neighboring cells, creating strange hybrids. The most aggressive types of cancer cells invade local tissues and/or break loose and travel in the bloodstream to distant parts of the body (metastasize).

Hundreds of thousands of different mutations have been discovered in cancerous cells, but it is actually rare to find genetic mutations in healthy cells because healthy cells have stable DNA. DNA is the most important molecule in the body so evolution has made sure it is well-protected. The DNA of healthy cells is not fragile. It would not have survived all this time if it were. There are even “caretaker genes” that are designed to maintain and repair defects in DNA, because lots of things in the natural environment can injure DNA—even things we think of as healthy, such as sunlight and vegetables.

Cancer cells have unstable DNA, which mutates easily and is therefore constantly changing. This is why there are so many mutations found in cancer cells. This “genomic instability” is viewed as a strong suit by scientists who believe in the mutation theory. They think that the tumor cells keep mutating to improve themselves, and that the ones with the most clever mutations are the ones which survive best and reproduce best (Darwinism—survival of the fittest). They think of cancerous cells as invincible—as stronger, faster, and smarter than healthy cells. But this isn’t true.

Yes, most tumor cells are growing faster than most of their healthy neighboring cells, but this is not because they are speedier. It’s because they are unregulated. All the healthy cells around them are capable of growing just as fast, but there are checks and balances in place to prevent them from growing willy-nilly. When necessary, they can grow just as fast, if not faster than tumor cells do. For example, when the liver is injured and healthy cells need to grow rapidly to replace the injured cells, their growth rate is the same as for liver cancer cells during tumor progression.

Tumor cells are more vulnerable than healthy cells. This is how radiation and chemotherapy work. Radiation and chemotherapy are toxic to all cells, cancerous or not, but they are more toxic to tumor cells. If tumor cells were more robust than normal cells, these therapies would kill off all your healthy cells and only the big ugly tumor would survive. Instead, people are treated to the brink of destruction with chemicals and radiation while doctors cross their fingers hoping more tumor cells will die than healthy cells, and that patients will survive the therapy.

Fragile DNA is not flexible enough or coordinated enough to respond to challenges. It is, after all, the stability of healthy DNA that allows our cells to adapt to stressful environments. Tumor cells are also more sensitive to heat (fever) and to starvation. When the body is stressed, the tumor cells are the first ones to go. These are not supervillain clones.

Just because cancer cells have lots of mutations doesn’t necessarily mean that mutations cause cancer. Seyfried argues that mutations are just red herrings (no disrespect to the herring community intended).

Poking holes in the mutation theory

The “oncogenic paradox” refers to this puzzle:

• A huge variety of things in the world—from viruses to radiation to chemicals to oxidation—can damage DNA and cause mutations. Seyfried quotes Nobel-prize winner Albert Szent-Györgyi: “It is getting more and more difficult to find something that is not carcinogenic.”
• There are hundreds of thousands of unique mutations associated with tumors. A single colon cancer cell can contain 11,000 mutations! The sheer number and type of mutations found in cancer cells are so serious that they would cause a healthy embryo to spontaneously abort, yet cancer cells somehow soldier on.
• The transformation of a healthy cell into a cancerous cell (malignant transformation) happens in the very same specific way every time.

How can all of these different and unpredictable events leading to all of those random mutations always cause exactly the same outcome? That’s like saying no matter how you attack an orc—whether you stab him in the belly with a sword, throw a rock at his head, or push him off a cliff—his left arm always falls off. Preposterous.

No specific mutation is a reliable marker for any one type of cancer

There is not one example of a mutation that causes the same type of cancer every time. Even those mutations most strongly associated with certain cancers only cause cancer in certain people.

Cancer cells within the very same tumor can have different mutation patterns.

Mutated genes thought to be strongly associated with cancer (“oncogenes”) sometimes do promote tumor growth, but sometimes they inhibit tumor growth, and sometimes they even do both.

Transplant experiments make the strongest case

Here’s the thing: if you transplant mutated cancer cell DNA into a healthy cell, the healthy cell almost never becomes cancerous.1 Only 2 out of 24 experiments were successful in transforming normal cells into cancer cells (and scientists couldn’t be sure that viral contamination wasn’t to blame). These results essentially kill the mutation theory dead on the spot.

The war on cancer

Just think about it: if cancer is a genetic disease, based on hundreds of thousands of mutations, what are we supposed to do, create hundreds of thousands of different drugs to treat it?

President Nixon declared war on cancer 40 years ago. The mutation theory of cancer has been solidly in place and guiding research since 1981, yet despite the enormous amounts of money, time, and energy that have been poured into cancer research since, we continue to lose the war against this killer disease. Fifteen-hundred Americans die every day from cancer. Researchers now place hope in the Cancer Genome Project, which they see as the shining future of cancer treatment. They have already started using the genetic fingerprints of cancer to design expensive, high-tech drugs that specifically target the unique DNA pattern of individual cancer cells. More than 700 of these smart bombs have been developed so far, yet none of them have saved a single life. The vast majority of whatever progress we have made against cancer has been due to identification of and education about lifestyle risk factors (such as smoking), not due to advances based on genetic theories.

Seyfried argues that the reason why we are making so little progress is because we are fighting the wrong enemy. Genes, he argues, are not the enemy, and they are not in the driver’s seat. Instead, they are innocent victims of the cancer. They are damaged, destabilized, and randomly mutated by the cancerous process. But if genetic mutations do not cause cancer, what does? How do cancer cells get by with all of these mutations? What keeps them going? And what causes all of these mutations in the first place?

In the next article in the series, “What Causes Cancer: Part II,” I explain the role of mitochondria in our cells and the significant link between damaged mitochondria and cancer.

To read my detailed critique of the World Health Organization’s 2015 report claiming that red meat causes cancer: “WHO Says Meat Causes Cancer“

Thomas Seyfried PhD, a brain cancer researcher with over 25 years of experience in the field, gave a groundbreaking presentation about cancer at the Ancestral Health Symposium held at Harvard Law School this past August. The three main take-home points of his talk:

1. Cancer is not caused by genetic mutations
2. Cancer is a mitochondrial disease
3. Cancer can be treated with ketogenic diets

The gene theory of cancer

In case your basic biology is rusty: our genes are made of DNA—coils of coded information that tell our cells exactly how to build all the proteins they need to conduct their daily business. These blueprints have to be flexible, because cells need different proteins under different circumstances. Cells must be able to adapt to various conditions, such as stress, injury, infection, temperature changes, and food supply. So, genes contain lots of special controls that can be turned on and off, depending on what’s going on in and around the cell.

I was taught in medical school that cancer is about genes going haywire—something evil comes along, like a toxic chemical or a beam of radiation, attacks your DNA, and poof—you’ve got cancer (unless you are a cartoon character, in which case you develop superpowers). Mutant cells start dividing like crazy and taking over your body. I was also taught that the way to get rid of cancer is to flood it with toxic chemicals and radiation . . . hmmm . . .

The company line is that cancer is caused by mutations (changes) in DNA that transform healthy, well-behaved cells into reckless, ravenous, immortal renegades. These mutations hijack the set of instructions encoded in the cells’ DNA, and scientists think these mutations cause cells to go wild.

Differences between healthy cells and cancer cells

Cancer cells are very different from normal cells. They grow independently, ignoring the anti-growth signals and death cues that would normally keep healthy cells from getting out of control. Cancer cells create their own blood supply and can divide forever. They lose many of the physical features of their mother cells; they are usually smaller, and may be disfigured or even shapeless. Sometimes they fuse with each other or with neighboring cells, creating strange hybrids. The most aggressive types of cancer cells invade local tissues and/or break loose and travel in the bloodstream to distant parts of the body (metastasize).

Hundreds of thousands of different mutations have been discovered in cancerous cells, but it is actually rare to find genetic mutations in healthy cells because healthy cells have stable DNA. DNA is the most important molecule in the body so evolution has made sure it is well-protected. The DNA of healthy cells is not fragile. It would not have survived all this time if it were. There are even “caretaker genes” that are designed to maintain and repair defects in DNA, because lots of things in the natural environment can injure DNA—even things we think of as healthy, such as sunlight and vegetables.

Cancer cells have unstable DNA, which mutates easily and is therefore constantly changing. This is why there are so many mutations found in cancer cells. This “genomic instability” is viewed as a strong suit by scientists who believe in the mutation theory. They think that the tumor cells keep mutating to improve themselves, and that the ones with the most clever mutations are the ones which survive best and reproduce best (Darwinism—survival of the fittest). They think of cancerous cells as invincible—as stronger, faster, and smarter than healthy cells. But this isn’t true.

Yes, most tumor cells are growing faster than most of their healthy neighboring cells, but this is not because they are speedier. It’s because they are unregulated. All the healthy cells around them are capable of growing just as fast, but there are checks and balances in place to prevent them from growing willy-nilly. When necessary, they can grow just as fast, if not faster than tumor cells do. For example, when the liver is injured and healthy cells need to grow rapidly to replace the injured cells, their growth rate is the same as for liver cancer cells during tumor progression.

Tumor cells are more vulnerable than healthy cells. This is how radiation and chemotherapy work. Radiation and chemotherapy are toxic to all cells, cancerous or not, but they are more toxic to tumor cells. If tumor cells were more robust than normal cells, these therapies would kill off all your healthy cells and only the big ugly tumor would survive. Instead, people are treated to the brink of destruction with chemicals and radiation while doctors cross their fingers hoping more tumor cells will die than healthy cells, and that patients will survive the therapy.

Fragile DNA is not flexible enough or coordinated enough to respond to challenges. It is, after all, the stability of healthy DNA that allows our cells to adapt to stressful environments. Tumor cells are also more sensitive to heat (fever) and to starvation. When the body is stressed, the tumor cells are the first ones to go. These are not supervillain clones.

Just because cancer cells have lots of mutations doesn’t necessarily mean that mutations cause cancer. Seyfried argues that mutations are just red herrings (no disrespect to the herring community intended).

Poking holes in the mutation theory

The “oncogenic paradox” refers to this puzzle:

• A huge variety of things in the world—from viruses to radiation to chemicals to oxidation—can damage DNA and cause mutations. Seyfried quotes Nobel-prize winner Albert Szent-Györgyi: “It is getting more and more difficult to find something that is not carcinogenic.”
• There are hundreds of thousands of unique mutations associated with tumors. A single colon cancer cell can contain 11,000 mutations! The sheer number and type of mutations found in cancer cells are so serious that they would cause a healthy embryo to spontaneously abort, yet cancer cells somehow soldier on.
• The transformation of a healthy cell into a cancerous cell (malignant transformation) happens in the very same specific way every time.

How can all of these different and unpredictable events leading to all of those random mutations always cause exactly the same outcome? That’s like saying no matter how you attack an orc—whether you stab him in the belly with a sword, throw a rock at his head, or push him off a cliff—his left arm always falls off. Preposterous.

No specific mutation is a reliable marker for any one type of cancer

There is not one example of a mutation that causes the same type of cancer every time. Even those mutations most strongly associated with certain cancers only cause cancer in certain people.

Cancer cells within the very same tumor can have different mutation patterns.

Mutated genes thought to be strongly associated with cancer (“oncogenes”) sometimes do promote tumor growth, but sometimes they inhibit tumor growth, and sometimes they even do both.

Transplant experiments make the strongest case

Here’s the thing: if you transplant mutated cancer cell DNA into a healthy cell, the healthy cell almost never becomes cancerous.1 Only 2 out of 24 experiments were successful in transforming normal cells into cancer cells (and scientists couldn’t be sure that viral contamination wasn’t to blame). These results essentially kill the mutation theory dead on the spot.

The war on cancer

Just think about it: if cancer is a genetic disease, based on hundreds of thousands of mutations, what are we supposed to do, create hundreds of thousands of different drugs to treat it?

President Nixon declared war on cancer 40 years ago. The mutation theory of cancer has been solidly in place and guiding research since 1981, yet despite the enormous amounts of money, time, and energy that have been poured into cancer research since, we continue to lose the war against this killer disease. Fifteen-hundred Americans die every day from cancer. Researchers now place hope in the Cancer Genome Project, which they see as the shining future of cancer treatment. They have already started using the genetic fingerprints of cancer to design expensive, high-tech drugs that specifically target the unique DNA pattern of individual cancer cells. More than 700 of these smart bombs have been developed so far, yet none of them have saved a single life. The vast majority of whatever progress we have made against cancer has been due to identification of and education about lifestyle risk factors (such as smoking), not due to advances based on genetic theories.

Seyfried argues that the reason why we are making so little progress is because we are fighting the wrong enemy. Genes, he argues, are not the enemy, and they are not in the driver’s seat. Instead, they are innocent victims of the cancer. They are damaged, destabilized, and randomly mutated by the cancerous process. But if genetic mutations do not cause cancer, what does? How do cancer cells get by with all of these mutations? What keeps them going? And what causes all of these mutations in the first place?

In the next article in the series, “What Causes Cancer: Part II,” I explain the role of mitochondria in our cells and the significant link between damaged mitochondria and cancer.

To read my detailed critique of the World Health Organization’s 2015 report claiming that red meat causes cancer: “WHO Says Meat Causes Cancer“

Nightshades have a reputation as bad actors in a variety of chronic conditions, such as arthritis, fibromyalgia, and IBS. But what do we really know about how these foods affect our health?

Meet the nightshade (solanaceae) family

• Tomatoes
• Tomatillos
• Eggplant
• Potatoes
• Goji Berries
• Tobacco
• Peppers (bell peppers, chili peppers, paprika, tamales, tomatillos, pimentos, cayenne, etc)

At first glance, the nightshades may look like a random collection of foods that couldn’t possibly be related. However, every nightshade plant produces fruits that all sport that same adorable little green elfish hat. Of the foods above, only tomatoes, eggplants, goji berries and peppers are “fruits” (the potato is a tuber and tobacco is a leaf). The fruits of potato and tobacco plants wear the same telltale hat, but we don’t eat the fruits of those plants.

Glycoalkaloids

Glycoalkaloids are natural pesticides produced by nightshade plants. Glycoalkaloids are bitter compounds which are found throughout the plant, but their concentrations are especially high in leaves, flowers, and unripe fruits. They are there to defend plants against bacteria, fungi, viruses, and insects.

Cherries, apples, and sugar beets also contain small amounts of glycoalkaloid even though they are not nightshades.

Vegetable violence

Glycoalkaloids act as invisible hand grenades. They bind strongly to the cholesterol in the cell membranes of predators, and in so doing, they disrupt the structure of those membranes, causing cells to leak or burst open upon contact.

Glycoalkaloids are neurotoxins. They block the enzyme cholinesterase. This enzyme is responsible for breaking down acetylcholine, a vital neurotransmitter that carries signals between nerve cells and muscle cells. When this important enzyme is blocked, acetylcholine can accumulate and electrically overstimulate the predator’s muscle cells. This can lead to paralysis, convulsions, respiratory arrest, and death. Military “nerve gases” work exactly the same way.

Ok, so glycoalkaloids are clearly nightmarish compounds for the cells of tiny creatures daring to munch upon nightshade plants, but what do we know about their effects on human health?

Nightshade glycoalkaloid health “benefits”

Health benefits? From a pesticide? Hmmm . . .

Since most people believe plant compounds are good for humans, when scientists conduct experiments with plant extracts, they are more likely to look for health benefits than health risks.

Glycoalkaloids are anti-inflammatory. Glycoalkaloids have been shown to reduce inflammation in laboratory animals. This is likely due to the fact that glycoalkaloids are structurally similar to compounds called glucocorticoids, which have well-known anti-inflammatory properties. Familiar examples of glucocorticoids include cortisol (our body’s natural stress hormone), and Prednisone, a commonly-prescribed anti-inflammatory medicine. It should be noted, however, that just because glycoalkaloids or glucocorticoids can reduce inflammation doesn’t mean they are always good for you. Prednisone is not something most of us should be taking every day, because it has numerous damaging side effects, and elevated levels of natural cortisol in our bodies weaken our immune system and slow our metabolism.

Glycoalkaloids kill bacteria and viruses. It should also not be surprising that glycoalkaloids have been shown in laboratory studies to possess antibiotic and antiviral properties, since this is what nature designed them for.

Glycoalkaloids have anti-cancer properties. In laboratory (in vitro) studies, glycoalkaloids can trigger cancer cells to self-destruct. This process is called “apoptosis.” Unfortunately, they can also cause healthy non-cancerous cells to do the same thing. Cancer studies in live animals and humans (in vivo) have not yet been conducted. The problem with so many anti-cancer plant compounds is that they are double-edged swords, killing both cancer cells and healthy cells alike:

“The undifferentiating destruction of both cancer and noncancerous cell lines . . . leads to questions of therapeutic uses of glycoalkaloids due to safety considerations. However, it is difficult to translate the results of an in vivo trial in vitro. Therefore, both animal and human experiments are essential to confirm or disprove the in vivo data observed in these studies.” [Milner 2011].

Health risks of nightshade glycoalkaloids

• Glycoalkaloids destroy cell membranes. Research has shown that glycoalkaloids can burst open the membranes of red blood cells and mitochondria (our cells’ energy generators). Some scientists have wondered whether glycoalkaloids could be one potential cause for ‘leaky gut’ syndromes due to their ability to poke holes in cells:

“Glycoalkaloids, normally available while eating potatoes, embed themselves and disrupt epithelial barrier integrity in a dose-dependent fashion in both cell culture models and in sheets of mammalian intestine. . . . [A]nimals with the genetic predisposition to develop IBD, demonstrated a greater degree of small intestinal epithelial barrier disruption and inflammation when their epithelium was exposed to the potato glycoalkaloids chaconine and solanine.” [Patel 2002]

• Glycoalkaloids cause birth defects in laboratory animals.

Nightshades and mental health

Due to widespread pro-plant food bias, the vast majority of scientific studies of nightshades explore their potential benefits rather than their downsides, so we do not have the studies we wish to have about how these interesting foods actually affect our well-being.

However, there have been plenty of documented cases of nightshade toxicity that demonstrate to us how poisonous they can be to our central nervous system—capable of causing severe neuropsychiatric side effects in human beings:

“In cases of mild glycoalkaloid poisoning symptoms include headache, vomiting, and diarrhea. Neurological symptoms were also reported, including apathy, restlessness, drowsiness, mental confusion, rambling, incoherence, stupor, hallucinations, dizziness, trembling, and visual disturbances.” [Milner 2011]

In a group of children who suffered from solanine poisoning as a result of eating potatoes that had been in storage for too long, severe psychiatric side effects were observed:

“The largest series of solanine poisoning involved an English day school where 78 schoolboys developed diarrhea and vomiting after eating potatoes stored since the summer term. Symptoms began 7-19 hours after ingestion with vomiting, diarrhea, anorexia, and malaise. Of the 78 boys, 17 were admitted to the hospital. Other symptoms included fever (88%), altered mental status (drowsiness, confusion, delirium) (82%), restlessness (47%), headache (29%), and hallucinations (23%). Three boys were seriously ill with hypotension, tachycardia [rapid heart rate], and stupor out of proportion to fluid and electrolyte imbalance. These boys were discharged 6-11 days after admission, and they had nonspecific symptoms and visual blurring for several weeks after release from the hospital.” [Barceloux 2009]

Keep in mind that these reactions just happened to be recorded due to their severity. We have no documented information about how everyday consumption of nightshades affects sensitive individuals, only numerous on-line personal accounts of mental health problems such as anxiety, panic, and insomnia that were alleviated by removal of nightshades from the diet. I personally experience profound insomnia and mild panic symptoms when I eat nightshades, which makes sense because glycoalkaloids overstimulate the nervous system.

If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article “5 Foods Proven to Cause Anxiety and Insomnia.”

Fruits vs vegetables: here we go again!

Those of you who are familiar with my philosophy about plant foods know that I believe that when it comes to our health, vegetables are far less trustworthy than edible fruits. Nightshades make this point nicely. [Watch my Ancestral Health Symposium video about vegetables vs. fruits if you are curious about my vegetable philosophy.]

As you will see below, even though nightshade fruits contain glycoalkaloids, they either contain lower amounts of these potentially toxic compounds or contain gentler versions of them.

Luckily, most of the edible nightshades—eggplant, tomatoes, goji and peppers—are fruits (fruits by definition contain seeds). Tobacco is a nightshade vegetable, but it is typically smoked, not eaten, so the only nightshade vegetable humans consume is the beloved potato.

Potato glycoalkaloids

All potatoes are nightshades except for sweet potatoes and yams.

Potato plants make two glycoalkaloids: alpha-chaconine and alpha-solanine. These are the most toxic glycoalkaloids found in the edible nightshade family. Alpha-chaconine is actually more potent than alpha-solanine, but solanine has been studied much more thoroughly.

There are numerous cases of livestock deaths from eating raw potatoes, potato berries, and potato leaves, but people don’t eat these things. However, there are well-documented reports of people getting glycoalkaloid poisoning from potatoes, typically from eating improperly stored, green, or sprouting potatoes. At low doses, humans can experience gastrointestinal symptoms, such as vomiting and diarrhea. At higher doses, much more serious symptoms can occur, including fever, low blood pressure, confusion, and other neurological problems. At very high doses, glycoalkaloids are fatal.

Another reason why many people may not be bothered by potatoes is that glycoalkaloids are very poorly absorbed by the gastrointestinal tract, so, if you have a healthy digestive tract, most of the glycoalkaloid won’t make it into your bloodstream. However, if you eat potatoes every day, levels can build up over time and accumulate in the body’s tissues and organs, because it takes many days for them to be cleared. Also, since glycoalkaloids have the ability to burst cells open, they can theoretically cause damage to the cells that line your digestive system as they are passing through (this has been proven in animal studies but there are no human studies, to my knowledge).

Due to known toxicity, the FDA limits the glycoalkaloid content in potatoes to a maximum of 200 mg/kg potatoes (91 mg/lb). Human studies show that doses as low as 1 mg glycoalkaloid per kg body weight can be toxic, and that doses as low as 3 mg/kg can be fatal. This means that, if you weigh 150 lbs, doses as low as 68 mg could be toxic, and doses as low as 202 mg could be fatal.

Glycoalkaloid levels of a few prepared potato products are available [Milner 2006]:

• Potato chips, 1 oz bag: 0.36 to 0.88 mg chaconine and 0.29 to 1.4 mg solanine. Total glycoalkaloid concentrations range from 2.7 to 12.4 mg per bag.
• Fried potato skins, 4 oz: 4.4 to 13.6 mg chaconine and 2.0 to 9.5 mg solanine. Total glycoalkaloid concentrations range from 6.4 to 23.1 mg per 4 oz serving.

Potato processing 101 

The vast majority of glycoalkaloid is in the potato skin, so peeling will remove virtually all of it. Glycoalkaloid levels can be dangerously high in unripe and sprouting potatoes; any greenish areas or “eyes” should be removed or avoided.

Glycoalkaloids survive most types of cooking and processing. In fact, deep frying will increase levels if the oil isn’t changed frequently, so fried products such as potato skins and french fries can contain relatively high amounts:

“Mechanical damage to potato tissue increases the concentration of glycoalkaloids available for consumption. In addition, frying potatoes at high temperatures does not inactivate but instead serves to preserve and concentrate glycoalkaloids within the potato, leaving them available for ingestion and delivery to the intestine.” [Patel 2002]

• Boiling—reduces glycoalkaloids by a few percentage points
• Microwaving—reduces glycoalkaloids by 15%
• Deep frying at 150C (300F)—no effect (McDonald’s uses 340F oil)
• Deep frying at 210C (410F)—reduces glycoalkaloid content by 40%

Tomato glycoalkaloids

Tomato nightshades include all types of tomatoes: cherry tomatoes, green tomatoes, yellow tomatoes and ripe red tomatoes.

Tomatoes produce two glycoalkaloids: alpha-tomatine and dehydrotomatine. The majority is in the form of alpha-tomatine, so we’ll focus on that one here.

As tomatoes ripen, alpha-tomatine levels drop dramatically, from about 500 mg/kg in green tomatoes to about 5 mg/kg in ripe red tomatoes, or 2.3 mg/lb. [For those of you keeping score at home—that’s Fruits: 1, Veggies: 0.] Artificially ripened fruits may contain higher amounts than sun-ripened fruits.

Tomato glycoalkaloids are about 20 times less toxic than potato glycoalkaloids. (Fruits: 2, Veggies: 0). There are no dosage studies of tomatine in humans, but studies in mice tell us that 500 mg tomatine per 1 kg body weight (or 227 mg per pound) is the median lethal dose (LD50). This doesn’t tell us how much it would take to kill a 150 lb person; it only tells us that it would take 34 grams of tomatine to kill a 150-pound mouse. Since ripe tomatoes contain 5 mg/kg or 2.3 mg/lb of tomatine, it would take nearly 15,000 pounds of tomatoes to kill this Mighty Mouse (probably many fewer pounds if you were to simply hurl them in his general direction from across the room). Since green tomatoes contain 100 times more tomatine, it would only take 150 pounds of green tomatoes to kill the overgrown rodent. We do not understand the effect of low doses of tomatine over time on any type of animal, including humans.

Eggplant glycoalkaloids

Centuries ago, the common eggplant was referred to as “mad apple” due to belief that eating it regularly would cause mental illness. Eggplants produce two glycoalkaloids: alpha-solamargine and alpha-solasonine. Solamargine is more potent than solasonine.

Whereas potato glycoalkaloids are located mainly in the skin, in eggplants, glycoalkaloids are found primarily within the seeds and flesh; the peel contains negligible amounts.

The common eggplant (solanum melongena) contains 10-20 mg/kg (or 4.5 to 9 mg/lb of eggplant). Eggplant glycoalkaloids are considered relatively nontoxic compared to potato glycoalkaloids (Fruits: 3, Veggies: 0).

The median lethal dose (LD50) in rodents is 1.75 mg/kg. This means that it would take at least 13 pounds of eggplant to kill a 150 lb monster mouse. [Note to self—when facing a giant rodent in a dark alley, go for the eggplants, not the tomatoes].

Peppers

Red and green bell peppers contain less than 10 mg of glycoalkaloid per kg. This is a very small amount, so if you react badly to peppers, you are either very sensitive, or you are responding to other compounds within the peppers, such as the notoriously hot and spicy capsaicinoids.

What about goji berries?

Your guess is as good as mine . . . I could not locate any scientific information about glycoalkaloids in these foods.

Nightshades and nicotine

Nightshade foods also contain small amounts of nicotine, especially when unripe. Nicotine is much higher in tobacco leaves, of course. Scientists think that nicotine is a natural plant pesticide, although it is unclear exactly how it works to protect plants from invaders. The amount of nicotine in ripe nightshade foods ranges from 2 to 7 micrograms per kg of food. Nicotine is heat-stable, therefore it is found in prepared foods such as ketchup and French fries. The health effects of these small doses are not known, but some scientists wonder whether the nicotine content of these foods is why some people describe feeling addicted to them. In my opinion, it is more likely that the high carbohydrate content of those foods is responsible for their addictive properties.

Do you have nightshade sensitivity? 

As with any food sensitivity, the only way to find out is to remove nightshades from your diet for a couple of weeks or so to see if you feel better. There are ZERO scientific articles about nightshade sensitivity, chronic pain, or arthritis in the literature, however, the internet is full of anecdotal reports of people who have found that nightshades aggravate arthritis, fibromyalgia, or other chronic pain syndromes. I am personally very sensitive to nightshades; they cause me a variety of symptoms, most notably heartburn, difficulty concentrating, pounding heart, muscle/nerve/joint pain, and profound insomnia. Everyone is different, so as always, you’ll need to discover for yourself whether these foods may pose problems for your individual chemistry. However, given what we know about nightshade chemicals, common sense tells us that these foods are well worth exploring as potential culprits in pain syndromes, gastrointestinal syndromes, and neurologic/psychiatric symptoms.

If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article “5 Foods Proven to Cause Anxiety and Insomnia.”

Other food sensitivity syndromes

If nightshades aren’t your problem, you may be interested to know that there are many other foods which can cause real health issues for people.

• To read about foods that interfere with proper thyroid function, see my post “Foods that Cause Hypothyroidism.”
• To learn how aged, cured, fermented, smoked and processed foods can cause or worsen allergies, migraines, PMS/peri-menopausal symptoms, IBS, anxiety, or insomnia, read “Freshness Counts: Histamine Intolerance.”
• To learn which foods are most likely to cause acne, check out my post “The Secret to Outsmarting Your Acne.”
• To understand the risks of eating broccoli, kale, and other cruciferous vegetables, see my post “Is Broccoli Good For You?“
• To learn which foods are most likely to cause IBS check out “Common Constipation Culprits” and “Is Fructose Malabsorption Causing Your IBS?“

Nightshades have a reputation as bad actors in a variety of chronic conditions, such as arthritis, fibromyalgia, and IBS. But what do we really know about how these foods affect our health?

Meet the nightshade (solanaceae) family

• Tomatoes
• Tomatillos
• Eggplant
• Potatoes
• Goji Berries
• Tobacco
• Peppers (bell peppers, chili peppers, paprika, tamales, tomatillos, pimentos, cayenne, etc)

At first glance, the nightshades may look like a random collection of foods that couldn’t possibly be related. However, every nightshade plant produces fruits that all sport that same adorable little green elfish hat. Of the foods above, only tomatoes, eggplants, goji berries and peppers are “fruits” (the potato is a tuber and tobacco is a leaf). The fruits of potato and tobacco plants wear the same telltale hat, but we don’t eat the fruits of those plants.

Glycoalkaloids

Glycoalkaloids are natural pesticides produced by nightshade plants. Glycoalkaloids are bitter compounds which are found throughout the plant, but their concentrations are especially high in leaves, flowers, and unripe fruits. They are there to defend plants against bacteria, fungi, viruses, and insects.

Cherries, apples, and sugar beets also contain small amounts of glycoalkaloid even though they are not nightshades.

Vegetable violence

Glycoalkaloids act as invisible hand grenades. They bind strongly to the cholesterol in the cell membranes of predators, and in so doing, they disrupt the structure of those membranes, causing cells to leak or burst open upon contact.

Glycoalkaloids are neurotoxins. They block the enzyme cholinesterase. This enzyme is responsible for breaking down acetylcholine, a vital neurotransmitter that carries signals between nerve cells and muscle cells. When this important enzyme is blocked, acetylcholine can accumulate and electrically overstimulate the predator’s muscle cells. This can lead to paralysis, convulsions, respiratory arrest, and death. Military “nerve gases” work exactly the same way.

Ok, so glycoalkaloids are clearly nightmarish compounds for the cells of tiny creatures daring to munch upon nightshade plants, but what do we know about their effects on human health?

Nightshade glycoalkaloid health “benefits”

Health benefits? From a pesticide? Hmmm . . .

Since most people believe plant compounds are good for humans, when scientists conduct experiments with plant extracts, they are more likely to look for health benefits than health risks.

Glycoalkaloids are anti-inflammatory. Glycoalkaloids have been shown to reduce inflammation in laboratory animals. This is likely due to the fact that glycoalkaloids are structurally similar to compounds called glucocorticoids, which have well-known anti-inflammatory properties. Familiar examples of glucocorticoids include cortisol (our body’s natural stress hormone), and Prednisone, a commonly-prescribed anti-inflammatory medicine. It should be noted, however, that just because glycoalkaloids or glucocorticoids can reduce inflammation doesn’t mean they are always good for you. Prednisone is not something most of us should be taking every day, because it has numerous damaging side effects, and elevated levels of natural cortisol in our bodies weaken our immune system and slow our metabolism.

Glycoalkaloids kill bacteria and viruses. It should also not be surprising that glycoalkaloids have been shown in laboratory studies to possess antibiotic and antiviral properties, since this is what nature designed them for.

Glycoalkaloids have anti-cancer properties. In laboratory (in vitro) studies, glycoalkaloids can trigger cancer cells to self-destruct. This process is called “apoptosis.” Unfortunately, they can also cause healthy non-cancerous cells to do the same thing. Cancer studies in live animals and humans (in vivo) have not yet been conducted. The problem with so many anti-cancer plant compounds is that they are double-edged swords, killing both cancer cells and healthy cells alike:

“The undifferentiating destruction of both cancer and noncancerous cell lines . . . leads to questions of therapeutic uses of glycoalkaloids due to safety considerations. However, it is difficult to translate the results of an in vivo trial in vitro. Therefore, both animal and human experiments are essential to confirm or disprove the in vivo data observed in these studies.” [Milner 2011].

Health risks of nightshade glycoalkaloids

• Glycoalkaloids destroy cell membranes. Research has shown that glycoalkaloids can burst open the membranes of red blood cells and mitochondria (our cells’ energy generators). Some scientists have wondered whether glycoalkaloids could be one potential cause for ‘leaky gut’ syndromes due to their ability to poke holes in cells:

“Glycoalkaloids, normally available while eating potatoes, embed themselves and disrupt epithelial barrier integrity in a dose-dependent fashion in both cell culture models and in sheets of mammalian intestine. . . . [A]nimals with the genetic predisposition to develop IBD, demonstrated a greater degree of small intestinal epithelial barrier disruption and inflammation when their epithelium was exposed to the potato glycoalkaloids chaconine and solanine.” [Patel 2002]

• Glycoalkaloids cause birth defects in laboratory animals.

Nightshades and mental health

Due to widespread pro-plant food bias, the vast majority of scientific studies of nightshades explore their potential benefits rather than their downsides, so we do not have the studies we wish to have about how these interesting foods actually affect our well-being.

However, there have been plenty of documented cases of nightshade toxicity that demonstrate to us how poisonous they can be to our central nervous system—capable of causing severe neuropsychiatric side effects in human beings:

“In cases of mild glycoalkaloid poisoning symptoms include headache, vomiting, and diarrhea. Neurological symptoms were also reported, including apathy, restlessness, drowsiness, mental confusion, rambling, incoherence, stupor, hallucinations, dizziness, trembling, and visual disturbances.” [Milner 2011]

In a group of children who suffered from solanine poisoning as a result of eating potatoes that had been in storage for too long, severe psychiatric side effects were observed:

“The largest series of solanine poisoning involved an English day school where 78 schoolboys developed diarrhea and vomiting after eating potatoes stored since the summer term. Symptoms began 7-19 hours after ingestion with vomiting, diarrhea, anorexia, and malaise. Of the 78 boys, 17 were admitted to the hospital. Other symptoms included fever (88%), altered mental status (drowsiness, confusion, delirium) (82%), restlessness (47%), headache (29%), and hallucinations (23%). Three boys were seriously ill with hypotension, tachycardia [rapid heart rate], and stupor out of proportion to fluid and electrolyte imbalance. These boys were discharged 6-11 days after admission, and they had nonspecific symptoms and visual blurring for several weeks after release from the hospital.” [Barceloux 2009]

Keep in mind that these reactions just happened to be recorded due to their severity. We have no documented information about how everyday consumption of nightshades affects sensitive individuals, only numerous on-line personal accounts of mental health problems such as anxiety, panic, and insomnia that were alleviated by removal of nightshades from the diet. I personally experience profound insomnia and mild panic symptoms when I eat nightshades, which makes sense because glycoalkaloids overstimulate the nervous system.

If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article “5 Foods Proven to Cause Anxiety and Insomnia.”

Fruits vs vegetables: here we go again!

Those of you who are familiar with my philosophy about plant foods know that I believe that when it comes to our health, vegetables are far less trustworthy than edible fruits. Nightshades make this point nicely. [Watch my Ancestral Health Symposium video about vegetables vs. fruits if you are curious about my vegetable philosophy.]

As you will see below, even though nightshade fruits contain glycoalkaloids, they either contain lower amounts of these potentially toxic compounds or contain gentler versions of them.

Luckily, most of the edible nightshades—eggplant, tomatoes, goji and peppers—are fruits (fruits by definition contain seeds). Tobacco is a nightshade vegetable, but it is typically smoked, not eaten, so the only nightshade vegetable humans consume is the beloved potato.

Potato glycoalkaloids

All potatoes are nightshades except for sweet potatoes and yams.

Potato plants make two glycoalkaloids: alpha-chaconine and alpha-solanine. These are the most toxic glycoalkaloids found in the edible nightshade family. Alpha-chaconine is actually more potent than alpha-solanine, but solanine has been studied much more thoroughly.

There are numerous cases of livestock deaths from eating raw potatoes, potato berries, and potato leaves, but people don’t eat these things. However, there are well-documented reports of people getting glycoalkaloid poisoning from potatoes, typically from eating improperly stored, green, or sprouting potatoes. At low doses, humans can experience gastrointestinal symptoms, such as vomiting and diarrhea. At higher doses, much more serious symptoms can occur, including fever, low blood pressure, confusion, and other neurological problems. At very high doses, glycoalkaloids are fatal.

Another reason why many people may not be bothered by potatoes is that glycoalkaloids are very poorly absorbed by the gastrointestinal tract, so, if you have a healthy digestive tract, most of the glycoalkaloid won’t make it into your bloodstream. However, if you eat potatoes every day, levels can build up over time and accumulate in the body’s tissues and organs, because it takes many days for them to be cleared. Also, since glycoalkaloids have the ability to burst cells open, they can theoretically cause damage to the cells that line your digestive system as they are passing through (this has been proven in animal studies but there are no human studies, to my knowledge).

Due to known toxicity, the FDA limits the glycoalkaloid content in potatoes to a maximum of 200 mg/kg potatoes (91 mg/lb). Human studies show that doses as low as 1 mg glycoalkaloid per kg body weight can be toxic, and that doses as low as 3 mg/kg can be fatal. This means that, if you weigh 150 lbs, doses as low as 68 mg could be toxic, and doses as low as 202 mg could be fatal.

Glycoalkaloid levels of a few prepared potato products are available [Milner 2006]:

• Potato chips, 1 oz bag: 0.36 to 0.88 mg chaconine and 0.29 to 1.4 mg solanine. Total glycoalkaloid concentrations range from 2.7 to 12.4 mg per bag.
• Fried potato skins, 4 oz: 4.4 to 13.6 mg chaconine and 2.0 to 9.5 mg solanine. Total glycoalkaloid concentrations range from 6.4 to 23.1 mg per 4 oz serving.

Potato processing 101 

The vast majority of glycoalkaloid is in the potato skin, so peeling will remove virtually all of it. Glycoalkaloid levels can be dangerously high in unripe and sprouting potatoes; any greenish areas or “eyes” should be removed or avoided.

Glycoalkaloids survive most types of cooking and processing. In fact, deep frying will increase levels if the oil isn’t changed frequently, so fried products such as potato skins and french fries can contain relatively high amounts:

“Mechanical damage to potato tissue increases the concentration of glycoalkaloids available for consumption. In addition, frying potatoes at high temperatures does not inactivate but instead serves to preserve and concentrate glycoalkaloids within the potato, leaving them available for ingestion and delivery to the intestine.” [Patel 2002]

• Boiling—reduces glycoalkaloids by a few percentage points
• Microwaving—reduces glycoalkaloids by 15%
• Deep frying at 150C (300F)—no effect (McDonald’s uses 340F oil)
• Deep frying at 210C (410F)—reduces glycoalkaloid content by 40%

Tomato glycoalkaloids

Tomato nightshades include all types of tomatoes: cherry tomatoes, green tomatoes, yellow tomatoes and ripe red tomatoes.

Tomatoes produce two glycoalkaloids: alpha-tomatine and dehydrotomatine. The majority is in the form of alpha-tomatine, so we’ll focus on that one here.

As tomatoes ripen, alpha-tomatine levels drop dramatically, from about 500 mg/kg in green tomatoes to about 5 mg/kg in ripe red tomatoes, or 2.3 mg/lb. [For those of you keeping score at home—that’s Fruits: 1, Veggies: 0.] Artificially ripened fruits may contain higher amounts than sun-ripened fruits.

Tomato glycoalkaloids are about 20 times less toxic than potato glycoalkaloids. (Fruits: 2, Veggies: 0). There are no dosage studies of tomatine in humans, but studies in mice tell us that 500 mg tomatine per 1 kg body weight (or 227 mg per pound) is the median lethal dose (LD50). This doesn’t tell us how much it would take to kill a 150 lb person; it only tells us that it would take 34 grams of tomatine to kill a 150-pound mouse. Since ripe tomatoes contain 5 mg/kg or 2.3 mg/lb of tomatine, it would take nearly 15,000 pounds of tomatoes to kill this Mighty Mouse (probably many fewer pounds if you were to simply hurl them in his general direction from across the room). Since green tomatoes contain 100 times more tomatine, it would only take 150 pounds of green tomatoes to kill the overgrown rodent. We do not understand the effect of low doses of tomatine over time on any type of animal, including humans.

Eggplant glycoalkaloids

Centuries ago, the common eggplant was referred to as “mad apple” due to belief that eating it regularly would cause mental illness. Eggplants produce two glycoalkaloids: alpha-solamargine and alpha-solasonine. Solamargine is more potent than solasonine.

Whereas potato glycoalkaloids are located mainly in the skin, in eggplants, glycoalkaloids are found primarily within the seeds and flesh; the peel contains negligible amounts.

The common eggplant (solanum melongena) contains 10-20 mg/kg (or 4.5 to 9 mg/lb of eggplant). Eggplant glycoalkaloids are considered relatively nontoxic compared to potato glycoalkaloids (Fruits: 3, Veggies: 0).

The median lethal dose (LD50) in rodents is 1.75 mg/kg. This means that it would take at least 13 pounds of eggplant to kill a 150 lb monster mouse. [Note to self—when facing a giant rodent in a dark alley, go for the eggplants, not the tomatoes].

Peppers

Red and green bell peppers contain less than 10 mg of glycoalkaloid per kg. This is a very small amount, so if you react badly to peppers, you are either very sensitive, or you are responding to other compounds within the peppers, such as the notoriously hot and spicy capsaicinoids.

What about goji berries?

Your guess is as good as mine . . . I could not locate any scientific information about glycoalkaloids in these foods.

Nightshades and nicotine

Nightshade foods also contain small amounts of nicotine, especially when unripe. Nicotine is much higher in tobacco leaves, of course. Scientists think that nicotine is a natural plant pesticide, although it is unclear exactly how it works to protect plants from invaders. The amount of nicotine in ripe nightshade foods ranges from 2 to 7 micrograms per kg of food. Nicotine is heat-stable, therefore it is found in prepared foods such as ketchup and French fries. The health effects of these small doses are not known, but some scientists wonder whether the nicotine content of these foods is why some people describe feeling addicted to them. In my opinion, it is more likely that the high carbohydrate content of those foods is responsible for their addictive properties.

Do you have nightshade sensitivity? 

As with any food sensitivity, the only way to find out is to remove nightshades from your diet for a couple of weeks or so to see if you feel better. There are ZERO scientific articles about nightshade sensitivity, chronic pain, or arthritis in the literature, however, the internet is full of anecdotal reports of people who have found that nightshades aggravate arthritis, fibromyalgia, or other chronic pain syndromes. I am personally very sensitive to nightshades; they cause me a variety of symptoms, most notably heartburn, difficulty concentrating, pounding heart, muscle/nerve/joint pain, and profound insomnia. Everyone is different, so as always, you’ll need to discover for yourself whether these foods may pose problems for your individual chemistry. However, given what we know about nightshade chemicals, common sense tells us that these foods are well worth exploring as potential culprits in pain syndromes, gastrointestinal syndromes, and neurologic/psychiatric symptoms.

If you experience anxiety or insomnia and are curious to know more about nightshades and the other foods most likely to be contributing to your symptoms, I recommend you read my Psychology Today article “5 Foods Proven to Cause Anxiety and Insomnia.”

Other food sensitivity syndromes

If nightshades aren’t your problem, you may be interested to know that there are many other foods which can cause real health issues for people.

• To read about foods that interfere with proper thyroid function, see my post “Foods that Cause Hypothyroidism.”
• To learn how aged, cured, fermented, smoked and processed foods can cause or worsen allergies, migraines, PMS/peri-menopausal symptoms, IBS, anxiety, or insomnia, read “Freshness Counts: Histamine Intolerance.”
• To learn which foods are most likely to cause acne, check out my post “The Secret to Outsmarting Your Acne.”
• To understand the risks of eating broccoli, kale, and other cruciferous vegetables, see my post “Is Broccoli Good For You?“
• To learn which foods are most likely to cause IBS check out “Common Constipation Culprits” and “Is Fructose Malabsorption Causing Your IBS?“

Nectresse is a new sweetener marketed by McNeil Nutritionals, the manufacturers of Splenda. Unlike Splenda, Nectresse is made from all-natural ingredients and therefore may appeal to those who wish to cut calories and exposure to the damaging effects of sugar without having to resort to artificial sweeteners.

As you can see, the vast majority of Nectresse (2 grams or 83%) is actually erythritol, not Mogroside V. The erythritol, sugar, and molasses act as sweet fillers. Mogroside V is so intensely sweet you wouldn’t want a whole packet of it. [It is for this same reason that the main ingredient in Splenda is not super-sweet sucralose, but dextrose, which is added as a bulking agent.] In the U.S., foods can be labeled as zero-calorie if they contain fewer than 5 calories per serving, so we don’t know exactly how many calories are in a 2.4 gram packet of Nectresse, only that it has fewer than 5 calories. Below is a quote taken directly from the manufacturer’s website:

“Like other no-calorie sweeteners, NECTRESSE Sweetener contains a small amount of carbohydrate (1-2 grams per serving) from other food ingredients to provide needed volume and texture. These food ingredients, which include small amounts of erythritol, sugar, and molasses, contribute so few calories per serving that NECTRESSE Natural No Calorie Sweetener Products meet the FDA’s criteria for no-calorie foods (<5 calories/serving).”

What is erythritol?

Erythritol is produced by adding yeast to glucose (a simple sugar) and letting it ferment. [Erythritol does exist in small amounts in nature, as well; however it would be expensive and impractical to collect it in large quantities for mass consumption.] Compared to sugar, sugar alcohols are poorly absorbed into our bloodstream, which is why they tend to be lower in calories. Most sugar alcohols make it all the way to the large intestine, where they may be fermented by bacteria, which can cause gases, bloating, and diarrhea. Sugar alcohols are notorious for causing embarrassing gastrointestinal side effects, especially if eaten in large quantities; however erythritol is the sugar alcohol least likely to cause these problems.

What is Mogroside V? 

While it sounds like a great name for, say, a big ugly orc, Mogroside V is an intensely sweet compound, 300 to 400 times sweeter than sugar. It is isolated from the monkfruit, a round, green fruit which grows in southwestern China—it is called monkfruit because it was eaten by Chinese monks as early as the 13th century. It also goes by many other names, such as luo han guo (aka “lo han”), rakanka, and Siraitia Grosvenori Swingle. The monkfruit belongs to the Cucurbita family of fruits, which includes cucumbers, melons, pumpkins, squashes, and gourds.

Monkfruit itself is described as having an unpleasant, cloying flavor, inspiring mouth-watering adjectives such as “licorice-like” and “vegetable-like.” Fresh monkfruit goes bad very quickly, so it is typically sold dried. In Asia, monkfruit has long been thought of as a medicinal fruit, being used to treat common symptoms such as coughs, sore throats, and constipation. Mogroside V makes up 1% of the weight of a dried monkfruit. Mogroside V dissolves easily in water, is heat-stable (so it can be used for cooking), and has a shelf life of approximately three years at room temperature.

Monkfruit extracts have been used in sugar substitutes for more than 30 years. Other brand name sweeteners which contain monkfruit extract include:

• Fruit-Sweetness™ (BioVittoria)
• Lakanto® (Saraya)
• PureFruit™ (Tate and Lyle)
• PureLo® (BioVittoria)
• SweetLife (Renew Life®)
• Symple™ (Naturewise)

I personally do not like the taste of Nectresse—I find it intolerably bitter, just as I do Stevia extract. However, everyone’s taste buds are different, and I understand that many people like it.

How does the human body handle Mogroside V?

Your guess is as good as mine.

To my surprise, I was unable to locate a single scientific study of Mogroside V metabolism in humans. There are just a handful of studies of this compound, some of which are published only in Chinese. All studies available were either conducted in laboratory animals or under test tube conditions (in vitro) using isolated cells. Nevertheless, in July 2009, the FDA declared Mogroside V “GRAS” (generally recognized as safe) in response to an application by the New Zealand company BioVittoria [BioVittoria supplies the monkfruit extract used in Nectresse]. So, I wrote to the BioVittoria company requesting scientific information, and was delighted to receive very helpful information from a kind representative, including a detailed research report, complete with dozens of references.

Is Mogroside V safe for human consumption?

Probably.

The FDA did not conduct its own safety studies of Mogroside V, but rather relied on BioVittoria to conduct studies. BioVittoria convinced the FDA of the safety of Mogroside V based on:

• 2 unpublished studies in humans to determine blood glucose and liver enzymes
• Several feeding studies in laboratory animals (rats, dogs, mice)
• 2 in-vitro genotoxicity studies (both found Mogroside V to be noncarcinogenic)

The unpublished studies reportedly demonstrated that Mogroside V does not raise blood sugar in humans. Published animal studies conclude that Mogroside V actually has “anti-diabetic effects.” The following is an example of an animal study showcasing the “anti-diabetic” effects of Mogroside V.

Researchers compared two diets in rats with type II diabetes—one diet contained Mogroside V (4 g/kg) and one diet contained cellulose (4 g/kg) as a control. Rats that ate Mogroside V demonstrated increased insulin production and secretion, which improved blood sugar regulation. The researchers concluded that this was a good thing because it was proof of “anti-diabetic” effects of Mogroside V. But let’s think about this for a moment.

1. A dose of 4 g/kg is extremely high. The average human would have to eat about 250 grams of pure Mogroside V extract to match this dose—that is the equivalent of more than 250 packets of Nectresse per day. [Toxicity studies in mice suggest that, on average, it would take about 10 g/kg to kill a human being.]
2. Increased insulin production is not necessarily a good thing. In fact, hyperinsulinemia (high insulin level) is exactly what we want to avoid, as it is a well-established risk factor for numerous diseases of civilization. Insulin tells the body to make fat. Please see my Carbohydrates page for more information.
3. Both of the rat diets were unbelievably junky—loaded with refined carbohydrate:

• 53% corn starch
• 20% casein (milk protein)
• 10% sucrose
• 7% soybean oil
• 5% cellulose
• 5% vitamins and minerals

Poor rats. I doubt you could design a menu that is farther from the natural diet of a rat if your life depended on it. Changing anything about this diet was bound to be an improvement. These animals did not gain weight or eat more food on the Mogroside diet compared to the regular diet. However, given their atrocious diet, I’m not sure it would have been possible for them to experience more weight gain or higher appetites than they must have been experiencing already.

4. Studies in rats tell us that Mogroside V itself is not even absorbed into the bloodstream (we don’t know if it is absorbed by humans). Instead, a by-product called “Mogrol” was found in trace amounts in the bloodstream. It is thought that Mogrol may be responsible for the metabolic effects of monkfruit extract.

In short, these studies tell us nothing about the effects of typical doses of Mogroside V on the blood sugar and insulin levels of human beings.

Why even bother to question the safety of a natural fruit extract? Because there can be important differences in health effects between eating a whole food in its natural state and consuming unnaturally concentrated extracts from that same food. Fruit extracts are, by and large, far less likely to be harmful to humans than vegetable extracts, so that is reassuring. (For more information about fruits vs. vegetables, see my pages about fruits and/or vegetables.)

Bottom line about Nectresse and Mogroside V:

1. Most of Nectresse consists of erythritol, not Mogroside V, so if erythritol doesn’t agree with you, neither will Nectresse.
2. Taste a bit of Nectresse before purchasing large quantities to be sure you like it.
3. I find no evidence that Nectresse is harmful to humans—however this is only because there are no published studies of the effects of Nectresse on humans.
4. If we trust the unpublished human studies, which reportedly found that Mogroside V did not raise blood sugar levels, then that is a good thing. However, as with all sweeteners, what is true in a study may not be true for you, so the only way to know if Nectresse raises your blood sugar is to test your own blood sugar readings before and after eating it.
5. There are no studies of Mogroside V on the insulin levels of human beings. High doses of Mogroside V in animals causes insulin spikes, which is not necessarily a good thing. High insulin levels are a risk factor for increased appetite and weight gain. Those of you who eat a ketogenic diet should be aware that Nectresse may cause insulin spikes which could temporarily reduce your serum ketone levels, so you’ll need to monitor your ketones carefully when first trying Nectresse.
6. Overall, I doubt that Mogroside V poses significant problems for the average human, but there isn’t enough evidence to be sure. As with any substance, the only way to know how it affects your metabolism—including your appetite, weight, and blood sugar, is to do your own experiments. Is it safer than sugar? Probably.

What about you? Have you tried Nectresse? Do you like it? Do you respond well to it? I’d love to read about your experience in the comments below.

If you are interested in reducing the sugar in your diet, you may also want to check out my insulin resistance post that includes an infographic about how to identify hidden sugars in your diet as well as my refined carbohydrates list.

Acknowledgments:

I am very grateful to Mr. Paul Paslaski of BioVittoria for providing such helpful scientific information regarding Mogroside V.

Nectresse is a new sweetener marketed by McNeil Nutritionals, the manufacturers of Splenda. Unlike Splenda, Nectresse is made from all-natural ingredients and therefore may appeal to those who wish to cut calories and exposure to the damaging effects of sugar without having to resort to artificial sweeteners.

As you can see, the vast majority of Nectresse (2 grams or 83%) is actually erythritol, not Mogroside V. The erythritol, sugar, and molasses act as sweet fillers. Mogroside V is so intensely sweet you wouldn’t want a whole packet of it. [It is for this same reason that the main ingredient in Splenda is not super-sweet sucralose, but dextrose, which is added as a bulking agent.] In the U.S., foods can be labeled as zero-calorie if they contain fewer than 5 calories per serving, so we don’t know exactly how many calories are in a 2.4 gram packet of Nectresse, only that it has fewer than 5 calories. Below is a quote taken directly from the manufacturer’s website:

“Like other no-calorie sweeteners, NECTRESSE Sweetener contains a small amount of carbohydrate (1-2 grams per serving) from other food ingredients to provide needed volume and texture. These food ingredients, which include small amounts of erythritol, sugar, and molasses, contribute so few calories per serving that NECTRESSE Natural No Calorie Sweetener Products meet the FDA’s criteria for no-calorie foods (<5 calories/serving).”

What is erythritol?

Erythritol is produced by adding yeast to glucose (a simple sugar) and letting it ferment. [Erythritol does exist in small amounts in nature, as well; however it would be expensive and impractical to collect it in large quantities for mass consumption.] Compared to sugar, sugar alcohols are poorly absorbed into our bloodstream, which is why they tend to be lower in calories. Most sugar alcohols make it all the way to the large intestine, where they may be fermented by bacteria, which can cause gases, bloating, and diarrhea. Sugar alcohols are notorious for causing embarrassing gastrointestinal side effects, especially if eaten in large quantities; however erythritol is the sugar alcohol least likely to cause these problems.

What is Mogroside V? 

While it sounds like a great name for, say, a big ugly orc, Mogroside V is an intensely sweet compound, 300 to 400 times sweeter than sugar. It is isolated from the monkfruit, a round, green fruit which grows in southwestern China—it is called monkfruit because it was eaten by Chinese monks as early as the 13th century. It also goes by many other names, such as luo han guo (aka “lo han”), rakanka, and Siraitia Grosvenori Swingle. The monkfruit belongs to the Cucurbita family of fruits, which includes cucumbers, melons, pumpkins, squashes, and gourds.

Monkfruit itself is described as having an unpleasant, cloying flavor, inspiring mouth-watering adjectives such as “licorice-like” and “vegetable-like.” Fresh monkfruit goes bad very quickly, so it is typically sold dried. In Asia, monkfruit has long been thought of as a medicinal fruit, being used to treat common symptoms such as coughs, sore throats, and constipation. Mogroside V makes up 1% of the weight of a dried monkfruit. Mogroside V dissolves easily in water, is heat-stable (so it can be used for cooking), and has a shelf life of approximately three years at room temperature.

Monkfruit extracts have been used in sugar substitutes for more than 30 years. Other brand name sweeteners which contain monkfruit extract include:

• Fruit-Sweetness™ (BioVittoria)
• Lakanto® (Saraya)
• PureFruit™ (Tate and Lyle)
• PureLo® (BioVittoria)
• SweetLife (Renew Life®)
• Symple™ (Naturewise)

I personally do not like the taste of Nectresse—I find it intolerably bitter, just as I do Stevia extract. However, everyone’s taste buds are different, and I understand that many people like it.

How does the human body handle Mogroside V?

Your guess is as good as mine.

To my surprise, I was unable to locate a single scientific study of Mogroside V metabolism in humans. There are just a handful of studies of this compound, some of which are published only in Chinese. All studies available were either conducted in laboratory animals or under test tube conditions (in vitro) using isolated cells. Nevertheless, in July 2009, the FDA declared Mogroside V “GRAS” (generally recognized as safe) in response to an application by the New Zealand company BioVittoria [BioVittoria supplies the monkfruit extract used in Nectresse]. So, I wrote to the BioVittoria company requesting scientific information, and was delighted to receive very helpful information from a kind representative, including a detailed research report, complete with dozens of references.

Is Mogroside V safe for human consumption?

Probably.

The FDA did not conduct its own safety studies of Mogroside V, but rather relied on BioVittoria to conduct studies. BioVittoria convinced the FDA of the safety of Mogroside V based on:

• 2 unpublished studies in humans to determine blood glucose and liver enzymes
• Several feeding studies in laboratory animals (rats, dogs, mice)
• 2 in-vitro genotoxicity studies (both found Mogroside V to be noncarcinogenic)

The unpublished studies reportedly demonstrated that Mogroside V does not raise blood sugar in humans. Published animal studies conclude that Mogroside V actually has “anti-diabetic effects.” The following is an example of an animal study showcasing the “anti-diabetic” effects of Mogroside V.

Researchers compared two diets in rats with type II diabetes—one diet contained Mogroside V (4 g/kg) and one diet contained cellulose (4 g/kg) as a control. Rats that ate Mogroside V demonstrated increased insulin production and secretion, which improved blood sugar regulation. The researchers concluded that this was a good thing because it was proof of “anti-diabetic” effects of Mogroside V. But let’s think about this for a moment.

1. A dose of 4 g/kg is extremely high. The average human would have to eat about 250 grams of pure Mogroside V extract to match this dose—that is the equivalent of more than 250 packets of Nectresse per day. [Toxicity studies in mice suggest that, on average, it would take about 10 g/kg to kill a human being.]
2. Increased insulin production is not necessarily a good thing. In fact, hyperinsulinemia (high insulin level) is exactly what we want to avoid, as it is a well-established risk factor for numerous diseases of civilization. Insulin tells the body to make fat. Please see my Carbohydrates page for more information.
3. Both of the rat diets were unbelievably junky—loaded with refined carbohydrate:

• 53% corn starch
• 20% casein (milk protein)
• 10% sucrose
• 7% soybean oil
• 5% cellulose
• 5% vitamins and minerals

Poor rats. I doubt you could design a menu that is farther from the natural diet of a rat if your life depended on it. Changing anything about this diet was bound to be an improvement. These animals did not gain weight or eat more food on the Mogroside diet compared to the regular diet. However, given their atrocious diet, I’m not sure it would have been possible for them to experience more weight gain or higher appetites than they must have been experiencing already.

4. Studies in rats tell us that Mogroside V itself is not even absorbed into the bloodstream (we don’t know if it is absorbed by humans). Instead, a by-product called “Mogrol” was found in trace amounts in the bloodstream. It is thought that Mogrol may be responsible for the metabolic effects of monkfruit extract.

In short, these studies tell us nothing about the effects of typical doses of Mogroside V on the blood sugar and insulin levels of human beings.

Why even bother to question the safety of a natural fruit extract? Because there can be important differences in health effects between eating a whole food in its natural state and consuming unnaturally concentrated extracts from that same food. Fruit extracts are, by and large, far less likely to be harmful to humans than vegetable extracts, so that is reassuring. (For more information about fruits vs. vegetables, see my pages about fruits and/or vegetables.)

Bottom line about Nectresse and Mogroside V:

1. Most of Nectresse consists of erythritol, not Mogroside V, so if erythritol doesn’t agree with you, neither will Nectresse.
2. Taste a bit of Nectresse before purchasing large quantities to be sure you like it.
3. I find no evidence that Nectresse is harmful to humans—however this is only because there are no published studies of the effects of Nectresse on humans.
4. If we trust the unpublished human studies, which reportedly found that Mogroside V did not raise blood sugar levels, then that is a good thing. However, as with all sweeteners, what is true in a study may not be true for you, so the only way to know if Nectresse raises your blood sugar is to test your own blood sugar readings before and after eating it.
5. There are no studies of Mogroside V on the insulin levels of human beings. High doses of Mogroside V in animals causes insulin spikes, which is not necessarily a good thing. High insulin levels are a risk factor for increased appetite and weight gain. Those of you who eat a ketogenic diet should be aware that Nectresse may cause insulin spikes which could temporarily reduce your serum ketone levels, so you’ll need to monitor your ketones carefully when first trying Nectresse.
6. Overall, I doubt that Mogroside V poses significant problems for the average human, but there isn’t enough evidence to be sure. As with any substance, the only way to know how it affects your metabolism—including your appetite, weight, and blood sugar, is to do your own experiments. Is it safer than sugar? Probably.

What about you? Have you tried Nectresse? Do you like it? Do you respond well to it? I’d love to read about your experience in the comments below.

If you are interested in reducing the sugar in your diet, you may also want to check out my insulin resistance post that includes an infographic about how to identify hidden sugars in your diet as well as my refined carbohydrates list.

Acknowledgments:

I am very grateful to Mr. Paul Paslaski of BioVittoria for providing such helpful scientific information regarding Mogroside V.