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Consuming too much food can lead to obesity, while eating too little can result in insufficient micronutrients needed for important cellular functions. Dr. Cronise describes his extended, unsupplemented fast after which he observed no apparent metabolic changes, and he challenges the paradigm that nutrients need to be balanced daily. In this clip, Dr. Ray Cronise and Dr. Rhonda Patrick discuss the importance of diet in maximizing healthspan and longevity.
Rhonda: So, you getting to this dietary restriction without malnutrition, we have a lot to talk about with dietary restriction and its effects on the human physiology. But did you supplement with anything? Was this like, so this 21-day fast were there any vitamin, mineral supplements, like, along with that?
Ray: No, and that's the surprising thing. I'll show you my nutrient panel. Even lasting with 14 days, my vitamin D went up, it didn't go down because I was in sunny California, lying in the sun, that was beautiful. I wasn't deficient in anything. All my blood panels turned out normal. On day 7, I did around the clock amino acid panel, where I did all the amino acids in there, several metabolites that are in there. And of course, they tracked with the circadian day, just like you've talked about. They're not something that are fixed. This idea that we're eating protein and it's pumping in our bloods. It's always there. But they do cycle with the day.
Of course, things like alanine, which is mainly used for the gluconeogenesis, it went through the roof, lipids go through the roof. So, there's some changes, certainly some physiological changes, but I wasn't deficient in anything.
The idea that we have to have nutrition every day and this balanced meal, that's one of the things that I really want to challenge because I do think we need a comprehensive nutrient adequacy across the spectrum. It is probably measured in days or weeks, not every single day.
Rhonda: Yeah. So, in terms of, like, the micronutrients and certain micronutrients that are needed you're talking about B vitamins, vitamin K, selenium, zinc, magnesium, the question still remains, like, what is an adequate level because a lot of the RDAs that are set are set on, based off of animal studies that have been that have shown that deficiency can cause death. And so, like, the couple standard deviations above that are what are considered what you need.
But the question is, and this something that my mentor Bruce Ames has proposed and put out there and I know that you're familiar with, it's something that he calls Triage Theory. And that is, well, there's all these enzymes and proteins that require some of these micronutrients as cofactors that are not essential for short-term survival. So, if you're deficient in it, it doesn't matter right now because it's not needed right now. It's needed for a long-term survival, it's needed to repair damage that's constantly happening. It's needed to prevent things like cancer, Alzheimer's disease.
So, the question of deficiency in and of itself, I think, needs to be challenged. I think we don't really know how much of these certain micronutrients we need to make sure DNA repair enzymes are still working, to make sure our tumor-suppressor genes are working, to make sure that all our antioxidants are... You know all these pathways that need these micronutrients are getting their cofactors that they need to work optimally or to at least be working as we're aging. So, I think that's... If we look at something like a blood panel, I mean, "Well, we're not deficient." Based on what? Based on the short-term functions because we don't know, right?
Ray: Well, yeah, but at the same time, we also don't the consequences of over nutrition. You know, we get a massive excess of a biologically active compound in levels that we would never would have seen in nature. And we've seen it with vitamin E, we've seen it in vitamin D, we've seen it in some of the other ones. So, the question is here first if we stop thinking about our diet as a daily thing and start thinking it as a lifetime thing, then things change because there may be things that are very much something you do. I mean, you guys are in prime reproduction time.
So, to get fecundity to go up and be more fecund, we want to increase essential amino acids. We know that things like methionine, whatever, increase fecundity. At the same time, where I am, which I'm done with that process at 51 that I want to make sure that have longevity. And they're also negatively associated with longevity.
So what I feel like where we are right now, the science and things we can be doing in the next decade, is taking this body of knowledge and yes, we can start peeling the onion more and more and more mechanistically. And now, we've spread that to all the blogs and they're peeling the onion. But every now and then, they cut off and forget half of it. They just sort of put these technical words out there. But how do we bring it back that look at something more comprehensive? How do we look at healthspan, you know?
Before we lengthen life, we need to lengthen healthspan. And I'm saying that if we look at...if I'm not deficient... The average person thinks if they go without a meal, their metabolism is going to to crush, for example, right? And this will be... We'll finish with the micronutrients but we'll go to the macro level. But if they think that by skipping a meal something's going to happen or by somehow not including some food group or something in every single meal that somehow, they're going to be deficient. You know, the ubiquitous the evil words I've told you before: protein, carb, and fat. I hate them. If you get on my blog, you'll see why.
But no one's going to be deficient in protein, really. And if they're going to be deficient, it's going to be one of nine essential amino acids. We know what they are. We've studied them quite a bit. And the fact of the matter is that for the average person out there, we also know that those nine happen to be connected to longevity too. And no one is looking at that part.
So, my point is looking at this as a spectrum. So, originally, we looked at diet because of the economics of food and the scarcity of food. If you don't have enough, it's great that every single thing meets a certain minimum, right? So, when these rules of eating were developed, and we can look at some of those later because I have all of those USDA guidelines from the turn of the century, which are just fascinating. Because they actually said why they did it and today, they have different reasons but they say the same thing. And that's kind of spooky to think about. We've made up new reasons for the same explanations.
But anyway, if you look at what they said, if you think about the average person is spending 60% of their income on food. And when you're at a situation where you have a limited, if you look at this as a budget thing, more people may relate to it. If you're in a budget, and you're barely making off each month, every dollar counts. But the value of $100 to me and a billionaire, it's still a $100. So, the point is that every dollar counts the closer you get to what you're meeting your needs are.
So, this idea of balanced meals, and balanced diets, and balanced nutrition, always being deficient came at a time when people really were deficient. Deficient, deficient, deficient...enough to see the diseases that we've identified. Now, what you're saying...
Rhonda: Their gums were falling out because they're getting scurvy.
Ray: Right. Yeah, and where you're at and I am too is... Okay, now, in addition to that, not necessarily what we are deficient in, if I change the language and say, "What more can we get at the micronutrient types, the..."
Rhonda: What do you need?
Ray: ...all the phytochemicals to maximize and optimize our longevity. You know, there isn't any perfect diet. We're not designed to eat anything. We can eat everything and that's why we're spread everywhere. But I think, somehow, this construct of food, and the construct of the balanced meal, and the construct that it happens in a single setting versus spread out over days or weeks, where I think the body is... It's much more rational to me to think that the body deals with it several days and weeks and doesn't become deficient instantly. I think that's where the attention needs to focus.
And there's really no money right now to be made in that. I can't sell somebody something. I can't sell them more supplements. I can't sell them more trainings. I can't sell them more exercise. And so, it's kind of a trap. But I think there's people like you and I, and some of the collaborators I'm working with and yours too, that's just intellectually curious about it. But we need to bring it back to whole food, we got to bring it back to foods that... What can we get out of what we have? And then, what's leftover to supplement.
Rhonda: Right.
A nonessential amino acid that is able to be manufactured by the human body and not dietarily required. It is nevertheless found in a wide variety of foods, and is particularly concentrated in meats.
A type of intermittent fasting in which a person fasts every other day. On “fasting” days, dietary intake is limited to 0–25% of typical caloric intake; on “feeding” days, energy take is not restricted. Scientific evidence suggests that ADF results in weight loss and improved metabolic parameters and may be an effective weight loss strategy in humans.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.
A laboratory analysis performed on a blood sample obtained either from a needle or finger prick. Blood panel tests are often used in healthcare to determine disease, mineral content, pharmaceutical drug effectiveness, or organ function. Typical blood panels include a basic metabolic panel, lipid panel, or a complete blood count.
A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.
Any of a group of complex proteins or conjugated proteins that are produced by living cells and act as catalyst in specific biochemical reactions.
Amino acids that cannot be synthesized by the organism, but must be supplied via diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine.
The capacity to reproduce. Fecundity is related to fertility.
A metabolic pathway in which the liver produces glucose from non-carbohydrate substrates including glycogenic amino acids (from protein) and glycerol (from lipids).
The years of a person’s life spent free of disease.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A sulfur-containing amino acid that is a constituent of most proteins. It is an essential nutrient in the diet of vertebrates. Methionine restriction in lower organisms has been shown to extend lifespan.
Vitamins and minerals that are required by organisms throughout life in small quantities to orchestrate a range of physiological functions. The term micronutrients encompasses vitamins, minerals, essential amino acids, essential fatty acids.
Highly reactive molecules that have the ability to oxidize other molecules and cause them to lose electrons. Common oxidants are oxygen, hydrogen peroxide, and superoxide anion.
The daily nutrient goals for essentially all healthy people. RDAs are calculated by determining the Estimated Average Requirements (the average amount of nutrients that half of all healthy people in any given demographic need each day) and adding two standard deviations. This ensures that the RDAs exceed the requirements of approximately 97.5% of the population.
A disease caused by vitamin C deficiency. Scurvy is characterized by bleeding, swollen gums, poor wound healing, joint pain, and bruising. Clinical features of scurvy appear in a person in as little as 84 to 97 days of vitamin C depletion. As scurvy progresses, a person might experience shortness of breath, dry eyes, joint swelling, weakness, fatigue, and depression.
Theory proposed by Dr. Bruce Ames which proposes that when the body is deficient in a micronutrient it will allocate its scarce supply to enzymes necessary for short-term survival and reproduction at the cost of long-term survival enzymes. This may result in the acceleration of the aging process.
A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.
A fat-soluble vitamin. Vitamin E is the collective name for a group of eight fat-soluble compounds (alpha-, beta-, gamma-, & delta-tocopherol and alpha-, beta-, gamma-, & delta-tocotrienol) with distinctive antioxidant activities. Of these eight, only alpha- (α-) tocopherol meets human requirements. Vitamin E serves as an antioxidant that breaks the chain reaction formation of reactive free radicals. In doing so it becomes oxidized and loses its antioxidant capacity. Vitamin E also protects LDL from oxidation and maintains the integrity of cell membranes throughout the body. Dietary sources of vitamin E include nuts, seeds, eggs, and fatty fish, such as salmon.
A type of fat-soluble vitamin. Vitamin K is critical for blood clotting, bone metabolism, prevention of blood vessel mineralization, and regulation of various cellular functions. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form in the diet. Vitamin K2 molecules are synthesized by the gut microbiota and found in fermented foods and some animal products (especially liver). The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times.
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