The Chemistry of Sulforaphane and Human Diet

Prepare yourself for the most epic, deep dive into the carnivore diet that you've ever heard.

I recently listened to a physician named Paul Saladino debate research scientist Layne Norton about the carnivore diet on my friend Mark Bell's podcast. I was so intrigued by the episode that I decided to get Paul on my show to explore the science behind the carnivore diet, carnivore diet do's and don'ts, and whether the carnivore diet is a true, sustainable, natural, ancestral nutrition approach or just a dietary fad.

During this show, we cover: -Why Paul is a raving fan of salmon roe...17:15

• Humans cannot make Omega 3 fatty acids
  • Omega 3's in salmon roe are in the phospholipid form
  • Salmon roe crosses the blood brain barrier more efficiently than in the triglyceride or ethyl ester form (which you'll find in most fish oil capsules)
• Two tbsps of salmon roe gives you the DHA without being exposed to the metals
• Benefit of getting a nutrient from a food vs. from a supplement
• Concern with oxidation in fish oil:
  • Look for certificate of analysis
  • Look at levels of lipid peroxides
  • Not nearly as much oxidation in eggs than the fish

-Why Paul doesn't consume black pepper...21:15

• A central principle of the carnivorous diet: plants are not put on the earth to serve humans
• Develop potentially toxic compounds to defend themselves from other animals
• A peppercorn is the seed of a plant
  • The seeds are where a higher concentration of pesticides and toxins reside
  • Pepper contains a compound called piperine, which inhibits UDP glucuronosyltransferase
• In essence: black pepper inhibits our body's natural detoxification process.
• Piperine is added to curcumin supplements to increase the level of curcumin you can absorb
• We don't actually use these molecules in human biochemistry
  • Used to activate certain pathways to produce our own antioxidants (which is glutathione)
• Plants induce Nrf2, while simultaneously doing toxic things to our bodies
• Sulforaphane is considered to be a highly beneficial molecule as a precursor to glutathione pathways
  • But is known to be a goitrogen (meaning it can induce hypothyroidism)
• Key take away: You can simulate the benefits of eating plants by eating meat and living a healthy lifestyle

-Why Paul refused a cup of Kion Coffee when offered by Ben...30:45

• Coffee is felt to be beneficial because of a couple of polyphenolic compounds: chloragenic acid and caffeic acid
  • These have been found to be clastogenic (DNA damage)
• A coffee bean is the seed of a plant, which contains toxins as a natural defense mechanism
• Very few animals eat those seeds

-Aren't plants like exercise, where you need them, but too much can be harmful?...26:05

• Hormesis is potential benefit of plants
• Sulforaphane:
  • Is linked to hypothyroidism
  • Depends on one's baseline level of iodine consumption
  • Does not exist in a plant
  • Glucoraphanin is converted into sulforaphane by Myrosinase
    • Highest levels are found in broccoli seeds and sprouts
• Humans are "facultative carnivores" meaning we can get everything we need from meat without ingesting the toxins found in plants.

-Storage organs in plants that result in larger brains and smaller guts...46:35

• Richard Wrangham
• Tubers
  • Fairly toxic generally speaking
  • Ancestral (non-hybridized) tubers aren't as valuable to humans due to size, appearance, etc.
  • Developed big brains by eating bone marrow and brains of animals (as scavengers)
  • No DHA, or fatty acids in a tuber
  • Macronutrients for short term survival; micronutrients for long term survival
  • Tubers have macronutrients, but not micronutrients
• Fossils of homo erectus found near water: algae, DHA, other micronutrients
• Just because tubers were efficacious for our ancestors doesn't mean we should choose them today
  • Animals provide all the micronutrients we need in the most bioavailable forms
  • The ultimate multivitamin for a human would be an animal

-Why plants may not be necessary, could be harmful to the gut, and are "survival food"...50:50

• Vilhjalmur Stefansson: Lived with Inuit people for a year
  • Observed they ate plants only when "real foods" i.e. animals weren't available
• Book: 100 Million Years of Food by Stephen Lee
• Even though humans have made plants more digestible via sprouting, fermenting, etc. we should still opt for the ribeye steak.

-Whether a carnivorous diet is sustainable or ethical...53:53

• Eat the animal "nose to tail"
• Book: The Whole Beast by Fergus Henderson
• Muscle meat is high in methionine but low in glycine
• Best results come when we eat organs and tendons along with the muscle meat
  • Different nutrients in different parts of the animal
• Why Ben called the carnivore diet "lazy" on the Joe Rogan podcast
• Carbohydrate availability for the thyroid
  • Ancestors would eat the thyroid immediately after killing an animal
• Do you need plants to consume adequate amounts of vitamins and minerals?
  • Good amounts of Vitamin C in liver and in brain; whale blubber
  • Liver also has large amounts of carotenal, a precursor to Vitamin A
  • Quercetin doesn't directly contribute to human biochemistry
  • You may not be able to get flavonoids from meat, but you may not need them at all

-How we would consume fiber on a carnivore diet, or if we even need it at all...1:06:40

• The debate between Paul Saladino and Layne Norton on the Mark Bell show
• Fiber is a "fairy tale"
  • Physician named Burkett in Tanzania
  • Tanzanians did not have as many cases of diverticulosis as Westerners
  • Erroneously equated high amounts of fiber intake with low cases of diverticulosis
  • The reverse is true
  • Applies to insoluble and soluble fiber
• "Healthy user bias" affects studies on fiber
  • People who eat less meat and more fiber, and engage in healthy activities
  • Stereotypical "meat eater": Steak, fries, cake, etc.

-Why Ben Greenfield is hesitant to embrace a full-on carnivore diet...1:13:50

• Variety is the spice of life (colors of food, tastes, etc.)
• Humans are "facultative carnivores"
  • Meant to eat animals, but can eat plants when animals are not available
  • Plants can contribute to life enjoyment if you choose to use them in your diet

-The carnivore diet and longevity...1:23:30

• Fallacy: centenarians live longer because of genetics. They live long in spite of what they eat.
• Theory of "blue zones" has been incorrectly interpreted
  • Not caused by diet (plants, legumes, etc.)
  • Clusters of longevity mutation in certain genes; improves insulin sensitivity, antioxidants, etc.
• High insulin sensitivity when carbs are cut out

-Carnivore vs. ketosis...1:28:45

• Three micronutrients: carbs, protein, fat
• We can run on two fuels: fat or carbs
  • fat that is stored or that you're eating
  • No such thing as an "essential carbohydrate"
• You can have a ketogenic diet that includes some plant foods that are potentially immunotoxic
• Carnivorous diet is by default a ketogenic because you're not eating plant-based carbs (trace amounts in meat)
• What about coconut oil and coconut cream?
  • Coconut has salicylates
  • Oil doesn't have actual coconut particles, but can have some salicylates
• Dairy: addictive to humans because it's the combination of fat and sugar; great for infants
  • It's why we crave ice cream
  • Rewarding but not satiating
  • Some cut out dairy, and find they're more satiated when eating meat

-The carnivore diet and amino intake...1:37:53

• Paul typically eats 3 pounds of meat per day
• No risk of developing cancer
  • Eating methionine without glycine becomes problematic
  • Bone broth and collagen are good sources of glycine

-Concern about constant activation of mTor on the carnivorous diet...1:41:00

• Concern about IGF-1 (insulin growth factor) levels raising on the diet
• Paul has found the opposite to be true
• Caloric restriction benefits come from sirtuin family of genes, which is activated by beta hydroxy butyrate
• Balances out because of the ketogenic state of the diet

-Whether a carnivorous diet is sustainable or ethical...1:45:30

• It's not practical for everyone to hunt their own meat
• Look at it from a population vs. individual basis
  • Answer questions pertaining to the individual before the population
  • Advances in technology contribute to increases in greenhouse gases (fossil fuel emissions)
  • Agriculture contributes ~8% of greenhouse gases; 3-4% is animal agriculture

-And much more... -Who is Paul Saladino?

Throughout the course of his life Paul Saladino has embarked on many adventures that have shaped his personal interests - including his unique, individualized approach to medicine. After studying chemistry at College of William he spent 6 years traveling and exploring. Highlights included a thru-hike of the Pacific Crest Trail from Mexico to Canada, a summer in the New Zealand backcountry, and 2 years skiing and climbing in Wyoming's Teton Mountains. He returned to academic studies after these adventures, first becoming a physician assistant and practicing in cardiology before training at the University of Arizona, obtaining his M.D. in 2015.

He is a certified Functional Medicine practitioner (IFMCP) through the Institute for Functional Medicine and will complete his residency in psychiatry at the University of Washington this June. When he is not researching connections between nutritional biochemistry and chronic disease he can be found in the frigid waters of the pacific northwest in search of the perfect wave.

Resources from this episode:

-My Facebook post on my "bastardized version" of the carnivore diet

-Paul Saladino's website

-Paul Saladino's YouTube channel

-The debate between Paul Saladino and Layne Norton on the Mark Bell show

-USWellnessMeats ribeye steaks - Use GREENFIELD for a 15% storewide - Offer good for up to 2 orders per customer. Excludes orders over 40 lbs, sale items, volume discounts, and gift certificates.

-Salmon roe

-Fred Provenza's book Nourishment

-Fiber and Colon Health On A Well-Formulated Ketogenic Diet: New Insights Question Its Role As An Unconditional Requirement

-The Kettle & Fire bone broth Ben drinks - Use code GREENFIELD for 10% off

Additional resources/research from Dr. Paul Saladino:  -Curcumin Curcumin (No RCTs which show benefit, potential toxicity)   "The Dark Side of Curcumin" -Piperine   Curcuminoids inhibit multiple human cytochromes P450 (CYP), UDP- glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes, while piperine is a relatively selective CYP3A4 inhibitor

Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine

Plant pesticides (claustogenicity of safrole[also in black pepper], caffeic acid, chlorogenic acid, glucosinolates [sulforaphane precursors])   -Cyanogenic glycosides in food   Cyanogenic glycosides in plant-based foods available in New Zealand

A Review of Cyanogenic Glycosides in Edible Plants

No association with meat consumption and colorectal cancer in Asia   No association of saturated fat and animal protein with colorectal cancer -Fiber -Diverticulosis study (worsened with increased fiber) Low fiber no association with constipation, diverticulosis Removal leads to improvement in constipation Lack of benefit in adenoma recurrence 

• Lack of benefit colorectal adenoma/cancer in women (NEJM)

• Dietary fiber lack of benefit in japanese populations with low fat intake

• Lack of effect of cereal supplement

• Lack of effect of high fiber/low fat diet

• Associated increase adenoma recurrence when combined with isphagula/calcium

Soluble fiber increases colon cancer in rodents Fiber does not increase alpha diversity -BHB and signalling/anti-aging mechanisms: Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer's Disease

Ketone bodies as signaling metabolites

β-hydroxybutyrate: Much more than a metabolite

D-ß-hydroxybutyrate: an anti-aging ketone body

Estrogenic properties of quercetin Effects of phyto-oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens Dangers of excess omega-6 (especially from seed oils)   Centenarians and genetic advantage   Salicylates (coconut)   Removal of flavonoid containing foods results in improved markers of oxidative stress   Green Tea catechins at obtainable dosing connected with liver injury (rise in transaminases) Oxalate toxicity -Casomorphin: A naturally occurring opioid peptide from cow's milk, beta-casomorphine-7, is a direct histamine releaser in man -Methionine/glycine ratio: Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet

Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins

Methionine and choline regulate the metabolic phenotype of a ketogenic diet

-Ketogenic Diet Improves Lifespan:

Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

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