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Could Eating Too Many Vegetables Wreck Your Health?

STORY AT-A-GLANCE This article was previously published July 7, 2019, and has been updated with new information.

Could Eating Too Many Vegetables Wreck Your Health?

Dr. Paul Saladino trained at the University of Arizona with a focus on integrative medicine. He completed his residency in psychiatry at the University of Washington in 2019, and is a certified functional medicine practitioner through the Institute for Functional Medicine. In this interview, Saladino discusses the surprising benefits of the carnivore diet, especially for those struggling with autoimmune disease. Initially, I was skeptical of the carnivore diet, but once I listened to Saladino's detailed analysis and justification for this approach, I changed my position and believe it is appropriate for a large number of individuals. While at the time of this interview, Saladino was still a resident-in-training, he's developed profound expertise in this area by attending medical school twice, and diving deep into the medical literature.

"I graduated from college in 1999. I went to the College of William and Mary,studied chemistry and biology and did a whole bunch of molecular biologyresearch there. My dad's a doctor, so I [was] steeped in medicine throughout mypre-career years and throughout my childhood …I've always been interested in the way that health and disease affected qualityof life and the way that food affected the way that I felt as a human being,"

Saladino says.

"I've been an athlete for most of my life, running and backcountry skiing andclimbing mountains and so on. I was always kind of tuned into connectionsbetween food and health and disease. But when I got out of college … I took sixyears off and just spent the time in the mountains, exploring and adventuring.Perhaps I already had this sort of seed within me of just questioning norms andasking interesting questions or being very curious. But that time certainly fedthat. I hiked the Pacific Crest Trail … 2,700 miles. I climbed mountainsthroughout the Pacific Northwest, the Rockies in Colorado. I got intomountaineering and backcountry skiing.
Eventually, I realized that I really loved biology. I was really curious about someof these health questions. I wanted to go back to school. My dad is … aninternist, an incredible man who spent so much of his life caring for patients.But I also saw him spend a lot of time working and not a lot of time being ableto achieve balance and real self-work …I went to physician assistant (PA) school at the George Washington University,and then started working in cardiology with a group of cardiologists in Bend,Oregon. Cardiology originally was a good fit for me because I thought I was arunner at the time … This is what maybe is unique about my training … I went tomedical school twice."

Looking for the Root of Disease

A PA can be likened to an accelerated shortcut to being a physician. They have nearly identical practicing privileges, although a PA works under the authority of a supervising physician. So, Saladino went through two years of basic clinical science twice, which helps explain his deep understanding and appreciation of the biological sciences. He admits that while his initial interest was primarily determining the benefits and drawbacks of various drug treatments, he quickly developed an interest in understanding the actual root of disease.

"I wanted to know how to change the course of a disease, how to get to the rootcause of the disease. I know this is what you're fascinated by too. It unites a lotof us in these fields. It's, 'What is causing a disease?' This is the mostinteresting question to me and medicine.That birthed my second career in medicine … Because I realized very quicklyinto my career as a PA that I was going to want to go back to medical school toget an M.D., to get a doctoral degree, to continue my training, to have the abilityto practice as a physician, and to do that practice from a perspective ofsomeone looking for root causes of diseases.That's really been my focus. I ended up working as a PA in cardiology for fouryears. At that point, I went back to medical school at the University of Arizona inTucson, which has a pretty strong history of integrative medicine … They havethe Center for Integrative Medicine there …As I looked at medicine differently, food seemed to be such a huge part. Thethings that we are putting into our body really seem to be a big part of whatcreated health and disease …Right now, I'm in my last month of my four years of residency at the Universityof Washington. I've got one month left to finish residency. But it was really thefirst seven years of my medical training after being a PA that kind of set thestage for this next sort of exploration, curiosity, realization for me …I had this incredible privilege to see medicine through the eyes of someone whohad been in the trenches. I thought, 'OK. Now I'm learning medicine again. Whatis going on here?' Every time I learned something, I thought, 'What is the rootcause here? What is going on?'What happened for me was this constant kind of disappointment, this constantsort of struggle realizing, 'The pharmaceuticals are incredible, but they're nottreating the root cause. People don't often get better' … I was looking for toolsthat worked … I had the suspicion that it was diet. What I'm learning is that theremay be an ideal diet for everyone, or it might be individualized. It might be someof both in there."

The Carnivore Diet

When Saladino discovered the carnivore diet, he'd already been contemplating ancestral norms and evolutionary ideas, asking questions such as: "Where have humans come from? How do we eat? What is the most congruent way of eating for humans that is going to give us optimal health?" He admits the idea of the carnivore diet is “super radical.” He first heard of the carnivore diet from Jordan Peterson on a Joe Rogan podcast. He talked about his daughter Mikhaila, who had a bad case of juvenile rheumatoid arthritis (JRA), which is an autoimmune infiammatory disease. She had multiple joint replacements at a young age, which crippled her. "She discovered this way of eating only animal meat," Saladino says, and over time, her symptoms improved.

"In medicine, we talk about case reports. I love case reports because I want tosee how things actually work at a real level,"

Saladino says.

"It was so striking tome that someone like Mikhaila could essentially reverse and completely healfrom JRA and then the depression that was connected with it, probably becauseof the concomitant immunologic and infiammatory mechanisms with thisradical dietary change.I thought, 'That is really striking. I want to study that.' Then Jordan Petersontalks about the fact that he had anxiety and sleep apnea and other issueshimself. They improved when he started eating an animal-based diet."

Might Plant Diets Trigger Autoimmune Problems in SomePeople?

Now, why would an animal-only diet be more effective than a plant-only diet? Everyone "knows" plant foods are good for you and a crucial part of a healthy diet. Saladino continues:

"I love that this notion just turned it all on its head. It just tipped everything overand I thought, 'Wait a minute. It kind of makes sense. Maybe plants don't wantto get eaten. Maybe plants aren't good for humans?' At the beginning, I was veryskeptical and I thought, 'I really need to dig into this,' and so I did …This fundamental premise, this idea that plants and humans, plants andherbivores or plants and animals have coevolved, and every life form really hasone goal. That's to push its DNA into the next species and to continue thelineage of that species.A mustard plant wants the mustard plant to continue. An oak tree wants the oaktree to continue. Life and ecology is this beautiful intermingling of all thesespecies working together but fighting and eating each other and trying to killeach other, but sometimes being symbiotic.This concept that 'Maybe plants don't want to get eaten after all,' maybe thisunconditional narrative that all plants are good for you all the time, maybe weshould question that. That's a pretty radical concept, because I think evenwithin the functional medicine sphere, there's this notion that all plants aregood for you and the more plants you eat, the better.But this counterculture, disruptive concept that for some people — perhaps forall of us, perhaps just for some people — plants can trigger autoimmunitythrough a variety of mechanisms is really intriguing."

The Plant Paradox

I've previously highlighted the work of Dr. Steven Gundry, who wrote the book “The Plant Paradox.” In it, he succinctly explains why and how plants, which we expect to be beneficial for us, can be harmful at times. Gundry's premise is based on the harmful effects of lectins — plant proteins, sometimes called sticky proteins or glyca-binding proteins — because they seek out and bind to certain sugar molecules on the surface of cells. Some — including wheat germ agglutinin (WGA), found in wheat and other grass-family seeds — bind to specific receptor sites on your intestinal mucosal cells and interfere with the absorption of nutrients across your intestinal wall. As such, they act as "antinutrients," and can have a detrimental effect on your gut microbiome by shifting the balance of your bacterial fiora. Saladino had already investigated lectins as a means to improve his own eczema.

"I think one of the ways that I differ greatly from mainstream medicine in myconceptualization … is I don't believe in 76,000 diseases. I believe in like fivediseases. Everybody manifests them a little differently. I kind of knew that myautoimmune disease was probably the same as almost everybody else'sautoimmune disease.If I could understand what was triggering my autoimmune disease, maybe thatwill be the first start of this journey, this first thread that I could pull on tounderstand what was causing other people's autoimmune diseases, becauseautoimmunity, infiammation, these are almost synonyms. If we can understandthat, we can help a lot of people.I was just going through this process. Gundry's work was a part of it. I think thatnow I would disagree with him on many issues … [He] has some great ideasabout lectins …I think … he's tried to create the lowest lectin, plant-based diet that he can with asmall amount of meat … But I think that he and many others aremisunderstanding a series of studies done in the '60s and '70s with rodents andmethionine overfeeding that suggested excess levels of methionine wouldshorten the lives of these rodents.Gundry and some other people have said, 'Animal protein shortens lives ofhumans' … I was actually a vegan 13 or 14 years ago. I explored that … Myimpression is that most of the plant-based physicians, when they're saying theanimal protein shortens lives, they're referring to these methionine studies."

Imbalance of Methionine-Glycine Ratio Is the Problem

As noted by Saladino, in studies where rodents are given very high amounts of methionine, a sulfur-containing amino acid found in animal protein, a shortening of lifespan is observed. However, rodent diets are quite different from human diets. Mice and rats are not eating salad and steak. They're given chow to which certain nutrient ratios have been added or subtracted. When the amount of methionine in the rat or mouse diet is increased by about 2%, lifespan starts to dwindle. The original conclusion was that excess methionine might shorten human lives as well, and some human biochemistry research suggest that might be the case. However, if you look at subsequent studies, you find there's more to the story.

"[W]hen they did the next study, they took the methionine out of the diet a littlebit. They did methionine restriction. What did they see? They saw lengtheningof the life of the rats … That was further strengthening their first hypothesis. Butthen the magical thing happened.They gave them a large amount of methionine or the same amount ofmethionine, 2% of the diet with more glycine. What did they see? They sawextension of the lifespan. Then they realized — and this is what I thinkeverybody's leaving out — that it's not about the excess methionine. It's aboutthe imbalance and the methionine-glycine ratio.We know this from human biochemistry. If you look at the folate cycle, if youlook at methylation, if you look at the way we handle methyl groups, methionineis a methyl-containing amino acid. We know that homocysteine is converted tomethionine by a series of enzymes. This involves the methylenetetrahydrofolate(MTHFR) gene, which makes L-5-methylfolate.Your body uses L-5-methylfolate with homocysteine and the enzymesmethionine synthase (MTR) and methionine synthase reductase (MTRR) … toadd a methyl group to homocysteine to make methionine. Methionine is theprecursor for S-adenosyl methionine (SAM-e). SAM-e does all thesemethylation reactions in the body.But what we know is that excess methionine is buffered by glycine. Our bodywill use glycine to buffer methionine. If we get too many methyl groups and wedon't have the corresponding amino acids to buffer them, the biochemistry canget kind of messed up.Then the hypothesis, which I think is fairly compelling, is that too many sulfur-containing amino acids can create oxidative stress. Homocysteine is a sulfur-containing amino acid. I think there's good evidence that too muchhomocysteine probably causes oxidative stress by the same mechanism.What we're looking at is a balance between sulfur- and nonsulfur-containingamino acids. We need the glycine, which doesn't have any sulfur, to sort ofbalance and buffer the methionine. There is this interesting concept that if weeat too much methionine, we will imbalance glycine.Glycine is such a crucial amino acid. If we use up all of our glycine to buffermethionine, we won't have enough glycine to make two very critical proteins:collagen and glutathione."

Can a Carnivore Diet Provide All the Nutrients You Need?

Glycine is the smallest and simplest of the amino acids. Methionine and glycine are found in muscle meat at a ratio of about 2% methionine and about 7% to 8% glycine. In connective tissue, you find about 0.9% methionine and about 23% to 24% glycine, which isn't surprising because connective tissue consists mostly of collagen. Collagen is typically constructed from three amino acids: glycine, proline and hydroxyproline, at a 1-to-1-to-1 ratio. So, there's a significant difference between collagenous tissue and muscle meat.

"When we are thinking about eating a carnivorous diet, I am a strong advocatefor this concept of nose-to-tail eating, this idea that evolutionarily, ourancestors were certainly eating the whole animal, both from a spiritualperspective or a respective perspective for the animal and from a functionalpragmatic perspective. They wanted all the calories and all the nutrients,"

Saladino says.

"If you look at an animal, there are unique nutrients in the muscle meat. There'sa whole unique set of nutrients in the liver, and … unique amino acidcomposition in the connective tissue. There are unique nutrients in the bones.There are unique nutrients in the bone marrow and the fatty tissues. You cansee this animal as this sort of fascinating partitioning of nutrients.The idea of a carnivore diet or a whole-foods, animal-based diet became muchmore viable for me when I realized … studying anthropology that our ancestorswere in fact eating the whole animal. Every indigenous culture that I'm aware ofon the planet that's living now eats the whole animal.Then you think, 'Now it makes sense.' It's not just about eating steak. You'rereally getting this incredibly diverse array of nutrients in the whole animal … Youcan get every single thing that we need. It's really interesting to kind of break itdown and say, 'You're getting calcium in the bones. You're getting copper tobalance the zinc in the liver. You're getting this B vitamin in the liver. You'regetting this B vitamin in the muscle meat.'But what we find is that we have to eat the whole animal. If we just eat themuscle meat, we're really going to be missing out on nutrients. But that's suchan incredible postulate to say, 'Wait a minute. I can get all the nutrients that Ineed as a human by eating an animal nose-to-tail?' That's incredible. It's like thebest multivitamin ever.I would argue further that animal-based nutrients are much more bioavailablethan plant-based nutrients. They're in the right ratio, which are incredible if youlook at zinc, copper, calcium and magnesium. Then it kind of makes sensewhen you think about it from an evolutionary perspective. A deer or an elephantis a mammal. They're much more similar to a human operating system, to ahuman physiology, than a plant is.We can get some nutrients from plants, but an animal looks so much more likeus, that it's so much more compatible with our biochemistry when we take it in.The last part of the equation is that we can do all that, eating animals nose-to-tail without any of the antinutrients … that might be present in plants.It appears that some people may be uniquely sensitive to those anti-nutrients.My hypothesis … is that may be the root cause for a lot of autoimmunity."

Organ Meats in a Pill

If you struggle with the idea of eating organ meats, you could consider a whole food supplement. There are now a few companies that provide desiccated organ tablets. Some of the better ones are sourcing grass fed animals from New Zealand, allowing you to get desiccated brain, liver, pancreas and spleen.

"A lot of people are finding improvements in histamine issues with kidney,"

Saladino says.

"The best thing would be to eat kidney, because it has diamineoxidase (DAO) …But a lot of people are taking the desiccated organ complex with kidney fromAncestral Supplements or another manufacturer and getting improvements inhistamine issues because of the DAO that's in that."

What About mTOR Activation?

One of my initial concerns, and one of the reasons why I seriously doubted the carnivore diet would be a good idea, is the chronic activation of mammalian target of rapamycin (mTOR), a protein-sensing pathway involved in aging. When mTOR is activated then autophagy is inhibited, and that is the last thing you want to do on a long-term basis, as it is a prescription for metabolic disaster. However, as I listened to Saladino's presentations, it became clear that it was a no-carb diet and would clearly put people into ketosis. And if they further restricted their eating window to six hours and did a one-day-a-week fast, there should be more than enough time to inhibit mTOR and activate autophagy. For quite some time I was overly fearful of eating too much protein and over activating mTOR activation as it can speed aging and decreases life span. Some people are even taking rapamycin supplements to continually suppress it. But you do need to activate mTOR now and then, especially if you want to have any hope of ever increasing your muscle mass. What I also came to realize is that activating mTOR and increasing muscle mass is even more important as you age. Sarcopenia or loss of muscle mass as you age can dramatically contribute to frailty. So, it is a fine balance.

Insulin Is Primary mTOR Activator When in Ketosis

As noted by Saladino, there's an important distinction to be made here, and that is that when you are in a ketogenic state, insulin is a far more profound activator of mTOR than leucine. Needless to say, a carnivore diet is about as low-carb (ketogenic) as you get. There's virtually no carbohydrates. You're going to be generating massive amounts of ketones as a result, and you'll already be in ketosis. The question is, can these two approaches — the carnivore diet and partial fasting to trigger autophagy — be successfully integrated? Based on Saladino's explanation of how the carnivore diet affects mTOR, it appears they might make for an excellent hybrid program.

"In a gross oversimplification, [mTOR] is kind of like the anabolic lever. It's the'build your body up' side of your metabolism. It's balanced by 5' adenosinemonophosphate-activated protein kinase (AMPK), which is the more catabolic.When we're eating … we're sort of activating mTOR … When we're not eating,we're generally triggering AMPK …There has to be a balance … What's fascinating to me about the mTOR story isthat when I really dug into this, the literature would suggest there are two waysto activate mTOR. There are different mechanisms, but they both do it. One ofthem is proteins, specifically leucine. One of them is insulin …In terms of insulin and leucine, if we compare those … insulin had a muchgreater effect on mTOR, turning it on. The insulin effect also acted much longer,on the order of three to four hours. Leucine certainly will turn mTOR on, but ithas a lesser effect. I think, relatively speaking, at the risk of putting a numberon it, it was about 30% less, and then it did it for only about 45 minutes to onehour.What we're seeing here is we can activate mTOR with protein, specificallyleucine load … But if we activate mTOR with leucine, it's kind of on and then offabout an hour later. If we activate mTOR with insulin, then it's going to be on forthree to four hours. People can leverage this in whatever direction they want.But with regard to a carnivore diet, some of the interesting discussion is aroundthe question, 'Will eating … nose to tail … over-activate mTOR?' I think what'sinteresting is it probably won't, if we look at the molecular mechanisms,because it will primarily be a leucine switch of mTOR that we're turning on. It'llbe on-off, on-off, rather than the insulin switch of mTOR.Relatively speaking here, I think there's an interesting possibility that if we'reeating carbohydrates, we're going to trigger more mTOR through the actions ofinsulin and the insulin-glucagon ratio than we are with protein. The carnivorediet is kind of like a unique example, because there's essentially nocarbohydrate.When we look at ketogenic diets, like a carnivore diet, we know that insulin isvery low … When we eat food, insulin is going to rise. But in a ketogenic state,we know that insulin and glucagon are going to rise together. That ratio is notreally going to change.This comes up a lot in discussions with people. They say, 'Isn't eating a lot ofprotein going to spike my insulin? Isn't eating a lot of protein going to turn ongluconeogenesis? My blood sugar is going to spike.' That's not what we see atall, especially on a carnivore diet, because the insulin and the glucagon aregoing to rise a little bit, and they rise concomitantly, so then the insulin-glucagon ratio doesn't change.When the insulin-glucagon ratio stays consistent, you're not really activatingmTOR through insulin. You're not getting a big insulin spike at all … If someone'snot in ketosis, if they're not fat-adapted and you eat a bunch of protein, yes,you're going to get a big spike in your insulin. That insulin-glucagon ratio isgoing to change drastically. But this is in stark contradistinction to the way thatinsulin responds when you're in a ketogenic state."

Carnivore Diet May Work Well With Partial Fasting Regimen

In summary, Saladino believes there's little risk of overactivating mTOR with leucine on a nose-to-tail carnivore diet along with appropriate time restricted eating and fasting. So, the answer to the question "can these two approaches — the carnivore diet and partial fasting to trigger autophagy — be successfully integrated?" the answer seems to be yes. From an evolutionary perspective, it seems clear humans have hunted animals for meat (although not necessarily exclusively). Mankind also fasted for periods of time.

"I think there's absolutely a role for intermittent fasting, time-restricted eating,longer fasts — 24, 48, 72 hours — where you really shut everything off and youturn on AMPK,"

Saladino says.

"You shut mTOR down permanently for a littlewhile, and then turn it back on with protein and meat …I would argue that the meat or the animal foods are a little bit more of a preciseswitch for mTOR. You can just be like, 'On, off, on, off.' Like I said, you canexercise, turn it on, get anabolic, work out, build muscle, regrow and then doother phases where you're breaking down, doing autophagy or apoptosis andtotally recycling your cells."

I've previously written many articles detailing the ins and outs of intermittent fasting and cyclical partial fasting. This is also the topic of my latest book, " KetoFast ." I've also written about the importance of eating your last meal at least three hours before bedtime. Aside from preventing the deterioration of your mitochondria, avoiding late-night eating will also help inhibit fat accumulation. NADPH creates fatty acids. If you eat food before you go to bed, thereby providing your body with energy that you're not using, then something must be done with that energy. Since you're not moving, your body stores it away for later use. To store the energy as fat, your body uses NADPH to make fatty acids. As a result of that creation, your NADPH levels plummet, thus reducing your body's ability to recharge your antioxidant structure. I think this may be one of the most important justifications for not eating three or four hours before bedtime.

Other Topics Covered in This Interview

Saladino covers a lot of ground in this interview — more than can be included in this written summary, so I encourage you to listen to the interview in its entirety. In it, we also cover the following topics, and consider the following questions: • The best use of polyphenols — Most polyphenols are plant-based, and are beneficial for autophagy and the activation of various metabolic pathways. Fisetin and quercetin are now used for senolytic therapy, leading-edge longevity strategies to remove senescent cells (cells that stop reproducing but are still active and create infiammatory molecules, typically cytokines that cause metabolic havoc). You don't need a large percentage of senescent cells to radically accelerate the aging process. • Is there a dark side to sulforaphane (the anticancer compound found in broccoli)? According to Saladino, there might be, as sulforaphane is actually a plant toxin and the brassica genus is a significant contributor to endemic goiter and cretinism (a prenatal condition caused by inadequate iodine). • Alternative ways to increase glutathione beside plant-based sulforaphane, such as heat stress, cold stress, exercise, fasting and nutritional ketosis. • How green smoothie cleanses can backfire by overloading on oxalates, and how you can mediate against oxalate toxicity by adding about 500 mg of powdered calcium citrate or magnesium citrate (which bind to oxalate and allow it to pass unabsorbed through your digestive tract) • What does Saladino's personal bloodwork look like after eight months on a nose-to- tail carnivore diet, and what does it say about its health effects?

More Information

By the time this interview airs, Saladino will have completed his residency and opened his private practice focusing on functional medicine for the treatment of psychiatric and nonpsychiatric ailments. You can learn more about Saladino and his practice on . He plans on doing virtual consultations as well, so you may benefit from his experience even if you're in another state. To schedule a virtual or in-person consultation, email him at . Saladino is also writing a book, and is starting to speak at various conferences. He'll be at KetoCon in Austin, in June 2019. He also has a podcast called "Fundamental Health With Paul Saladino M.D.," which you can find on iTunes, Stitcher, Spotify and YouTube. In closing, Saladino says:

"I think this is one of the conversations that I really like having … It's saying,'Hey. This is a radical thing. We really need to examine this carefully and doblood testing and make sure it's safe for people, because it seems to helppeople with autoimmune disease.'I've seen people with Crohn's and ulcerative colitis and eczema and psoriasisresolve, which is just mind-boggling … But the fiipside is you need to make sure[it's safe] … 'Are people going to get deficiencies?' I don't think so. I think there'san evolutionary basis for this. But how do we show this is safe and get somepilot studies going?Because it's my strengthening suspicion that this is going to be a very usefultool for us in the medical world moving forward … What I've learned aboutfunctional medicine is that it all starts in the gut. Every functional medicinedoctor has to be a gastroenterologist …I'm going to be treating patients in my practice who are psychiatric and non-psychiatric because I really think it's all connected … I'll be treating people withall sorts of conditions, from GI to autoimmune … I really believe that a lot ofpsychiatric illness is autoimmune in nature and that a big part of improving thatin the future is going to be treating people from that perspective, in a veryholistic way."

Editor's Note: This article was updated July 29, 2019, to correct an error on how to mediate against oxalate toxicity.

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