Cruciferous Vegetables - Sulforaphane
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“Cato the Elder (234-149bc), a Roman statesman, noted in his book about medical plants that cabbage, eaten crude with vinegar or cooked with oil or fat, banishes and cures all, ‘from crapulence after exceeding wine consumption up to serious diseases like cancer’.  He writes: ‘if a cancerous ulcer appears upon the breasts, apply a crushed cabbage leaf and it will make it well’”

​List of Cruciferous Vegetables:

  • Arugula
  • Bok choi
  • Broccoli
  • Broccoli  rabe
  • Broccoli Romanesco
  • Brussels sprout
  • Cabbage
  • Cauliflower
  • Chinese broccoli
  • Chinese cabbage
  • Collard greens
  • Daikon
  • Garden cress
  • Horseradish
  • Kale
  • Kohlrabi
  • Komatsuna
  • Land cress
  • Mizuna
  • Mustard – seeds and leaves
  • Pak choi
  • Radish
  • Rutabaga
  • Tatsoi
  • Turnips – root and greens
  • Wasabi
  • Watercress

Cruciferous vegetables contain phytochemicals, vitamins, minerals, and fiber that are important to your health
Sulforaphane – may reduce
  • Risk of cancer
  • Cardiovascular disease
  • Neurodegenerative diseases
  • Possibly slows the aging process
Isothiocyanates
  • Formed from the compounds glucosinolates through an enzyme myrosinase
    • Glucosinolates →→→→→→→ isothiocyanates
                                                       Myrosinase
  • Myrosinase is activated when cruciferous plant tissue is crushed, chopped or chewed
  • Myrosinase is inactivated from sustained high heat
  • Sulforaphane is a prominent isothiocyanate stands out because:
    • Large volume of scientific research
    • it’s potency
    • The glucosinolate that sulforaphane is formed from is glucoraphanin
    • Broccoli sprouts likely contain the greatest amount of glucoraphanin
    • Broccoli sprouts contain up to 100x’s as much glucoraphanin as broccoli heads
  • Isothiocyanates also activate phase 2 detoxification enzymes – causing them to be excreted
    • Mediated by the NRF2 pathway
    • Sulforaphane  is the most potent inducer of the NRF2 pathway
    • The NRF2 pathway is very important because it controls hundreds of genes by acting on the antioxidant response elements
    • Glutathione S-transferase (a phase 2 detoxification enzyme) are able to deactivate procarcinogens transforming them into water-soluble conjugates and then excreted in the urine and bile
      • Also reduces DNA damage by decreasing inflammation and decreasing reactive oxygen species
  • When people increase cruciferous vegetable consumption there is a corresponding increase in Glutathione S-transferase
    • The induction of Glutathione S-transferase is usually assumed to result in a decreased risk of cancer.
    • When participants consumed 300g of Brussel sprouts/day – Glutathione S-transferase circulating in plasma was increased by a factor of 1.4
      • Overall oxidative DNA damage decreased by 28%
        • Oxidative DNA damage is fundamental to the process of aging
        • Oxidative DNA damage initiates cancer
  • Sulforaphane and its precursor glucoraphanin can significantly increase the excretion of benzene
  • Participants given daily broccoli sprout beverage containing 262.5mg of glucoraphanin and about 7.1mg sulforaphane (135g fresh broccoli sprouts/day) increased the rate of excretion of benzene by 61% beginning on the 1st day of consuming the drink and continuing throughout the entire 12 week trial.
    • Sources of benzene cigarette smoke, air pollution (automobile exhaust)
    • Acrolein (another carcinogen) excretion increased 23% during the 12 week trial.
      • Acrolein also forms when carbohydrates, fats and proteins are heated.
  • NNK, a potent tobacco-specific pulmonary carcinogen is  detoxified through the action of a isothiocyanate found in water cress
  • An all-cause mortality study (not caused by accidents ) of 3442 deaths among women and 1951 deaths among men showed a 22% reduced mortality for the participants consuming the most cruciferous vegetables.
    • The reduced risk of death was mostly associated with cardiovascular disease which is still the #1 cause of death in the united states
    • 10g/day (BSP) broccoli sprout powder as supplementary treatment in type 2 diabetes could have favorable effects on lipid profiles and OX-LDL/LDL ratio, as risk factors for cardiovascular disease.
      • Lowered serum triglyceride by 18.7%
      • Lowered oxidized LDL by 13.5%
      • Nearly 20% drop in fasting blood sugar
      • 10g BSP = 40mg sulforaphane =100g fresh weight of BS
Sulforaphane
  • The most potent activator of the NRF2 pathway which regulates over 200 different genes
    • Antioxidant, anti-inflammatory genes, and genes that inactivate harmful compounds
  • Potent cancer preventative effects and likely effects the influence cardiovascular disease
  • Helps excrete carcinogens
  • Kills cancer cells and reduces cancer risk through multiple biochemical pathways
    • Deactivation of Phase 1 biotransformation enzymes – which are responsible for converting procarcinogens into carcinogens
    • Prevents the formation of DNA adducts – which is a type of DNA damage which can lead to cancer
      • Tobacco smoke is loaded with carcinogens that form DNA adducts
      • Eating at least 4.5 servings of cruciferous vegetables/month has been associated with a 55% reduced risk of lung cancer.
    • Increased expression of NQ01 within breast tissue
      • NQ01 prevents degradation of tumor suppressor protein p53
      • Over 50% of all adult cancers have a broken or mutated p53 gene
      • NQ01 also involved in detoxification
      • All occurs within 1 hour after consuming broccoli sprout extract from 3 day old sprouts
  • Sulforaphane inhibits the growth of breast cancer stem cells in mice
  • In rat studies sulforaphane has been shown to increase glutathione expression and increase antioxidant activity in endothelial cells that line blood vessels, and relaxes smooth muscle cells.
    • Sulforaphane reduces adhesive molecules (E-selectin) that are part of the atherosclerotic state that are activated by the inflammatory cascade.
  • FOXO3
    • A variant of FOXO3 has been shown to be associated with longevity in humans.
    • Increased expression associated with 2.7 fold increase of being a centenarian
    • Becoming a centenarian depends on keeping inflammation controlled
    • Including capability (both physical and cognitive abilities)
  • Sulforaphane shown in mice to regulate inflammation through NF-kappa-B
    • Reduced circulatory levels of IL-6
    • Resulting in reduced nerve damage
    • Healthy individuals given 14g/kg /day of cruciferous vegetables decreased plasma levels of IL-6 by 20%
    • BSP 40mg sulforaphane (100grams fresh sprouts)
      • reduced TNF alpha by 11%
      • reduced serum CRP (C-reactive protein) by 16%
      • in people with type 2 diabetes
  • Under normal conditions NFR2 is activated every 129 minutes
  • When stimulated by sulforaphane it is activated every 80 minutes
  • 61% increase
  • NRF2 regulates over 200 genes – many of these genes affect cellular aging
  • NRF2 protects against cancer – an age related disease
    • Deactivates carcinogens and increasing their excretion
    • Deactivating genes involved with inflammation
    • Activating anti-oxidant genes
  • Therefor NRF2 likely affects aging as well. Because oxidative stress, inflammation, and DNA damage are fundamental to aging and lead to our cells becoming senescent.
    • NRF2 lowers the cumulative damage occurring within cells which can accelerate telomere shortening.
    • Short telomeres lead to cellular senescence and premature aging
    • Telomeres are the repetitive DNA sequences and specialized proteins that form the distinctive structure that caps the ends of linear chromosomes
    • Telomeres allow cells to distinguish the chromosome ends from double strand DNA breaks. 
    • The telomeric structure prevents the degradation or fusion of chromosome ends, and thus is essential for maintaining the integrity and stability of eukaryotic genomes.
    • Telomere shortening is a rather elegant biomarker for cellular senescence.  
    • Our acquired or adaptive immune cells are more prone to senescence (immunosenescence)
    • More susceptible to infection as we age
    • Sulforaphane in mice demonstrated old mice were able to regain some of the lost function of the immune system
    • Humans (extrapolated dose) 20mg/day [43grams of fresh broccoli sprouts]
    • Age related hair loss is androgenetic alopecia
The majority of women with androgenetic - also called androgenic - alopecia have diffuse thinning on all areas of the scalp. (Men rarely have diffuse thinning but instead have more distinct patterns of baldness.) Some women have a combination of two pattern types.
  • Mediated through the production of dihydrotestosterone which slows the growth phase of the hair follicle decreasing the production of new hair
  • A study in mice showed hair regrowth with injected sulforaphane
    • 50% increase in hair regrowth
    • A decrease in dihydrotestosterone levels
Sulforaphane – and your Brain
  • May cross the Blood-Brain barrier
  • Benefits from lowering inflammation in the CNS
  • The NRF2 pathway = strongest defense against oxidative stress
  • Oxidative stress activates the NRF2 pathway
  • Oxidative stress contributes to many diseases
  • Broccoli sprouts 9mg-25mg was able to improve checklist scores in autism spectrum disorder (ASD) by 34%, significantly improve social interaction, verbal communication and behavior in one study
  • Another study showed 30mg/day of glucoraphanin (precursor of Sulforaphane) helped in a small number of patients with schizophrenia
  • Depression
    • One of the most common psychiatric illnesses in the world
    • About 10% of US adults are on a selective reuptake inhibitor (WHO)
    • Nutrition plays a large role in depression
      • By affecting the production or function of neurotransmitters
      • By affecting systemic inflammation, activating the immune system which affects brain function and neurotransmission
      • Proinflammatory cytokines (IL-1, IL-6, THF alpha, LPS) trigger activate the immune responses that affect neurotransmission.
  • Neurodegenerative disease
    • Reactive oxygen species (ROS) are the hallmarks of neurodegenerative disorders
      • Alzheimer’s
      • Parkinson’s        
      • Huntington’s
    • Inflammation (high oxidative stress) causes abnormal deposition of proteins in the brain tissue
    • Injection of Sulforaphane (NRF2 activator) has been shown to improve spatial working memory and short term memory in mice that had been injected with amyloid
    • Has been shown to reduce tremors and normalize dopamine levels in mice chemically induced Parkinson’s disease.
    • Has been shown to clear aggregates from the brains of mice that were genetically engineered to have Huntington’s disease.
    • Sulforaphane activates many heat shock proteins by increasing the levels of heat shock factor-1 (Hsf1) which is an activator of many heat shock proteins
      • The activation of heat shock proteins may be helpful in preventing deposition of proteins in the CNS thereby offering some protection against Alzheimer’s, Parkinson’s and Huntington’s diseases.
  • Traumatic Brian Injury (TBI)
    • Because of the pathophysiological involvement of oxidative stress and inflammatory disease processes (similar to Alzheimer’s, Parkinson’s and Huntington’s diseases)
    • Sulforaphane can be protective against TBI which has been shown in animals.
    • Injectable sulforaphane after TBI was shown to attenuate blood brain barrier (BBB) permeability and reduced cerebral edema if administered within 1 hour post injury.
    • Sulforaphane administered 15 minutes after a cerebral infarct causing ischemia caused a reduction in infarct volume (reduced size of necrotic tissue) 3 days later.
    • Neuron outgrowth (repair process following TBI) through the activation of NRF2
      • Obesity and type 2 diabetes can decrease the production of neurotrophic factors [neuronal plasticity (repair)]
      • Rats with diabetes showed reduced levels of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)
        • Experimentally reversed by administration of Sulforaphane
  • Duchenne muscular dystrophy
    • is a genetic disorder characterized by progressive muscle degeneration and weakness
    • caused by an absence of dystrophin, a protein that helps keep muscle cells intact
    • leads to premature death
    • corticosteroids is the only effective treatment, not a cure
      • In a mouse study injections of sulforaphane was shown to increase skeletal muscle mass, muscle force by 30%, and running distance by 20%
      • In a cell culture study sulforaphane was shown to inhibit Myostatin in muscle satellite cells which are an inhibitor of muscle growth.
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          Click on the image to see Dr. Rhona Patricks wonderful indepth YouTube video covering            the notes above. Her Website is ​https://www.foundmyfitness.com/