Ketosis is a natural procedure the human body goes through on a regular basis. This method provides the cells with energy from ketones if sugar isn’t readily available. A moderate degree of ketosis occurs when we skip a meal or two, do not consume many carbohydrates throughout the day or exercise for an extended amount of time. When there is an increased demand for energy and carbohydrates are not immediately available to meet that need, the human body will subsequently�begin to raise its ketone levels.
If carbohydrates continue to be limited for a considerable amount of time, ketone levels may increase further. These deeper degrees of ketosis provide many favorable effects throughout the entire body. These benefits can be taken advantage of by following the ketogenic diet. However, the majority of people are seldom in ketosis since the human body prefers to utilize sugar, or glucose, as its principal fuel supply. Below, we will discuss ketosis, ketones, and how these procedures work together to keep the cells healthy.
How Nutrients are Converted into Energy
The human body processes several kinds of nutrients to produce the energy it requires. Carbohydrates, proteins, and fats can be converted to energy in order to fuel various metabolic processes. If you consume high-carbohydrate foods or excessive amounts of protein, your cells will break these down into a simple sugar called glucose. This occurs because sugar provides the cells with the fastest source of ATP, which one of the main energy molecules required to fuel virtually every system within the human body.
By way of instance, more ATP means more cell energy and more calories result in more ATP. As a matter of fact, each calorie consumed from carbohydrates, proteins, and fats may be utilized to maximize ATP levels. The human body consumes a lot of these nutrients to maintain the proper function of all its structures. If you consume more than sufficient food, nevertheless, there’ll be too much sugar which your�system does not need. But, considering this, what does the human body do with all this excess sugar? Instead of eliminating excess calories which the body does not need, it will store them as fat where it can be used later once the cells require energy.
The human body stores energy in two ways:
Glycogenesis. Through this procedure, excess glucose is converted into glycogen, or the stored form of glucose,�which is stored in the liver and muscles. Researchers estimate that the entire human body stores about 2000 calories in the shape of muscle and liver glycogen. This generally means that glycogen levels will be used within 6 to 24 hours if no additional calories are consumed. An alternate system of energy storage may help sustain the human body when glycogen levels are reduced: lipogenesis.
Lipogenesis. When there are sufficient amounts of glycogen in the muscles and liver, any excess glucose is converted into fats and stores through a procedure called lipogenesis. Compared to our limited glycogen stores, our fat stores are almost infinite. These supply us with the capability to sustain ourselves for weeks to even months without enough food being available.
When food is limited and the intake of nutrients like carbohydrates are restricted, glycogenesis and lipogenesis is no longer active. Rather, these procedures are replaced with glycogenolysis and lipolysis which free�energy from glycogen and fat stores throughout the human body. However, something unexpected occurs when the cells no longer have stored sugar,�fat or glycogen. Fat will continue to be used as fuel but an alternate fuel source known as ketones is produced as well. Because of this, the process of ketosis occurs.
Why Does Ketosis Occur?
When you don’t have any access to foods, such as when you’re sleeping, fasting, or following the ketogenic diet, then the human body will convert some of its stored fat into exceptionally efficient energy molecules known as ketones. Ketones are synthesized following the entire breakdown of fats into fatty acids and glycerol, where we can thank our cell’s capacity to change metabolic pathways for this. Although fatty acids and glycerol are turned into fuel throughout the entire body, they’re not utilized as energy by brain cells.
Because these nutrients are converted into energy too slowly to support the function of the brain, sugar is still considered to be the principal source of fuel for the brain. This process also helps us understand why we create ketones. Without an alternate energy supply, the brain would be exceedingly vulnerable if we don’t consume enough calories. Our muscles would be broken down instantly and converted into sugar to feed our hungry brains. Without ketones, the human race would have most probably been extinct.
Low-carbohydrate modified ketogenic diets have been demonstrated to have many health benefits, including weight loss and the increased ability to help fight diabetes. These type of diets have a remarkable way of providing energy for the brain. Research studies have discovered that entering ketosis has the ability to reduce insulin levels, freeing fat from fat cells. Researchers have also shown that the ketogenic diet can have a significant metabolic advantage, which leads to more calories burned than with any other diet. Dr. Alex Jimenez D.C., C.C.S.T. Insight
The Way Ketones are Produced
The human body breaks down fat into fatty acids and glycerol which may be utilized for fuel in the cells directly but not by the brain. To fulfill the requirements of the brain, the fatty acids from fats and glycerol go through the liver where they’re then converted into glucose, or sugar, and ketones. Glycerol undergoes a process called gluconeogenesis, which transforms it into glucose, where fatty acids are converted to ketone bodies through a procedure called ketogenesis. As a consequence of ketogenesis, a ketone body called acetoacetate is generated. Acetoacetate is then converted to two different types of ketone bodies:
Beta-hydroxybutyrate (BHB). After being keto-adapted for several weeks, the cells will start to convert acetoacetate into BHB because it’s a more efficient source of fuel where it destroys an extra chemical reaction which provides more energy to the cell compared to acetoacetate. Research studies have demonstrated that the human body and brain favor utilizing BHB and acetoacetate for energy because the cells can utilize it 70 percent better than they can sugar or glucose.
Acetone.�This substance can occasionally be metabolized into glucose, however, it is largely eliminated as waste. This is what specifically provides the distinctly�smelling breath which many ketogenic dieters have�learned to understand.
Over time, the human body will release less surplus ketone bodies, or acetone, and, should you utilize keto sticks to monitor your degree of ketosis, you might believe it’s slowing down. As the brain burns off BHB as fuel, the cells attempt to present the brain with as much effective energy as they can. This is why long-term low-carbohydrate users won’t show profound levels of ketosis in their urine tests. As a matter of fact, long-term keto dieters can endure around 50 percent of their basal energy demands and 70 percent of their brain’s energy demands from ketones. Therefore, you shouldn’t allow the urine tests to fool you.
The Significance of Gluconeogenesis
Regardless of how�keto-adapted the human body may become, the cells will still require glucose to function properly. To satisfy the energy demands of the human mind and body which can’t be fulfilled by ketones, the liver will initiate�a process called gluconeogenesis. Amino acids in proteins and lactate in the muscles may also be transformed into glucose.
By converting amino acids, glycerol, and lactate into glucose, the liver can satisfy the glucose demands of the human body and brain during times of fasting and carbohydrate limitation. That is the reason why there’s not any crucial requirement for carbohydrates to be included in our diet. The liver will, generally, make sure to have sufficient sugar in the blood for your own cells to survive.
It’s important to remember, however, that certain variables, such as eating too much protein, may get in the way of ketosis and boost the demand for gluconeogenesis. Insulin levels and ketone production are closely connected. Protein sources, which are generally consumed on the ketogenic diet, can also increase insulin levels. In response to a rise in insulin levels, ketogenesis is downregulated, which raises the demand for gluconeogenesis to generate more sugar.
This is the reason why eating too much protein may impair your ability to enter ketosis. But this doesn’t necessarily mean you ought to limit your protein intake either. By restricting protein intake, your muscle cells will be employed to generate the sugar your body and brain demand for fuel. With proper guidance, you can consum the perfect quantity of protein your body needs to maintain muscle mass and fulfill your glucose needs when you’re on the road to ketosis.
Recognizing the Path to Ketosis
Almost all of our understanding behind ketosis originates from research studies on people who have fasted from all foods, not only from ketogenic dieters. However, we could make many inferences concerning the ketogenic diet out of what the researchers discovered from the research studies on fasting. First, let us look at the phases the body goes through during fasting:
Stage 1 – The glycogen depletion phase – 6 to 24 hours of fasting
In this phase, most energy is produced by glycogen. During this time, hormone levels begin to change, causing increases in gluconeogenesis and fat burning, however, ketone generation isn’t active yet.
Stage 2 – The gluconeogenic stage – 2 to 10 days of fasting
In this phase, glycogen is totally depleted and gluconeogenesis supplies the cells with energy. Ketones begin to be generated�at reduced levels. You will notice you have keto breath and are urinating more frequently due to greater acetone levels in your blood. The timeframe for this phase is so extensive (two to ten days) since it is dependent upon who is fasting. By way of instance, healthy men and obese people have a tendency to remain in the gluconeogenic phase for extended periods of time compared to healthy women.
Stage 3 – The ketogenic stage – after 2 days of fasting or more
This phase is characterized by a decrease in protein breakdown for energy through an increase in fat and ketone usage. At this phase, you will surely be in ketosis. Every individual can�enter this point at various rates based on lifestyle and genetic variables, their physical activity levels, and the number of times they fasted and/or restricted carbohydrates before. Whether you’re following the ketogenic diet or fasting, you may go through these phases, but this doesn’t guarantee the same benefits fasting as you do from the keto diet.
Ketogenic Diet Ketosis vs Starvation Ketosis
The ketosis which you experience on the ketogenic diet is considered to be a lot safer and healthier compared to the ketosis you get to when fasting. During the time you’re fasting, the human body doesn’t have any food resources, therefore it begins converting the protein from your muscles into sugar. This induces rapid muscle reduction.
The ketogenic diet, on the other hand, provides us with the healthiest and safest way to experience the advantages of ketosis. Limiting carbohydrates while keeping sufficient caloric intake from protein and fat permits the ketogenic procedure to sustain muscle tissue by employing ketosis and the ketone bodies we generate for fuel without having to utilize valuable muscle mass. Many research studies have discovered that ketones can also have an array of beneficial effects throughout the entire body too.
Ketoacidosis: The Bad Side of Ketosis
Ketoacidosis is a potentially lethal condition which occurs when excessive ketones accumulate in the blood. Some healthcare professionals may advise against increasing your ketone levels with the ketogenic diet because they fear you could enter ketoacidosis. The practice of ketosis is closely governed by the liver, and also the entire body infrequently generates more ketones then it requires for fuel. That is the reason why the ketogenic diet has been referred to as a safe and effective way to enter ketosis.
Ketoacidosis, on the other hand, is more likely to occur in type 1 and type 2 diabetics who don’t have their glucose under control. The mix of insulin deficiency and higher glucose levels, which are generally found in people with diabetes, produce a vicious cycle which causes ketones to build up in the blood. By limiting carbohydrates, nevertheless, healthy people and patients with diabetes may continue to keep their glucose under control and also experience the advantages of utilizing ketones for fuel.
Putting It All Together
Ketogenesis takes fatty acids from stored fat and transforms it into ketones. The ketones are subsequently released into the bloodstream. The procedure where the body burns off ketones for fuel is known as ketosis. However, not all cells can utilize ketones as fuel. Some cells will always utilize glucose to function accordingly. To satisfy the energy requirements which can’t be fulfilled by ketones, your liver utilizes a process called gluconeogenesis. Gluconeogenesis is the procedure where the liver converts glycerol from fatty acids, amino acids from proteins, and lactate from muscles,�into glucose. Collectively, ketogenesis and gluconeogenesis produce the ketones and glucose which fulfill all the body’s energy demands when food is not available or when carbohydrates�are limited.
Though ketones are well-known for being an alternate fuel supply, they supply us with several unique advantages too. The best and safest way to receive all the advantages of ketosis is by simply adhering to the ketogenic diet. In that way, you won’t encounter the chance of losing valuable muscle mass or inducing the potentially lethal condition of ketoacidosis. But, the ketogenic diet is somewhat more nuanced than a lot of men and women think. It is not just about restricting carbohydrates, it’s about making sure sufficient fat, protein, and overall calorie intake are consumed, which are ultimately vital.�The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion:�Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief. �
The nuclear erythroid 2-related factor 2 signaling pathway, best known as Nrf2, is a protective mechanism which functions as a “master regulator” of the human body’s antioxidant response. Nrf2 senses the levels of oxidative stress within the cells and triggers protective antioxidant mechanisms. While Nrf2 activation can have many benefits, Nrf2 “overexpression” can have several risks.
It appears that a balanced degree of NRF2 is essential towards preventing the overall development of a variety of diseases in addition to the general improvement of these health issues. However, NRF2 can also cause complications. The main cause behind NRF2 “overexpression” is due to a genetic mutation or a continuing chronic exposure to a chemical or oxidative stress, among others. Below, we will discuss the downsides of Nrf2 overexpression and demonstrate its mechanisms of action within the human body.
Cancer
Research studies found that mice that don’t express NRF2 are more inclined to develop cancer in response to physical and chemical stimulation. Similar research studies, however, showed that NRF2 over-activation, or even KEAP1 inactivation, can result in the exacerbation of certain cancers, particularly if those pathways have been interrupted. Overactive�NRF2 can occur through smoking, where continuous NRF2 activation is believed to be the cause of lung cancer in smokers. Nrf2 overexpression might cause cancerous cells not to self-destruct, while intermittent NRF2 activation can prevent cancerous cells from triggering toxin induction.
Additionally, because NRF2 overexpression increases the human body’s antioxidant ability to function beyond redox homeostasis, this boosts cell division and generates an unnatural pattern of DNA and histone methylation. This can ultimately�make�chemotherapy and radiotherapy less effective against cancer. Therefore, limiting NRF2 activation with substances like DIM, Luteolin, Zi Cao, or salinomycin could be ideal for patients with cancer although Nrf2 overactivation should not be considered to be the only cause for cancer. Nutrient deficiencies can affect genes, including NRF2. This might be one way as to how deficiencies contribute to tumors.
Liver
The overactivation of Nrf2, can also affect the function of specific organs in the human body. NRF2 overexpression can ultimately block the production of the insulin-like growth factor 1, or IGF-1, from the liver, which is essential for the regeneration of the liver.
Heart
While the acute overexpression of Nrf2 may have its benefits, continuous overexpression of NRF2 may cause long-term harmful effects on the heart, such as cardiomyopathy. NRF2 expression can be increased through high levels of cholesterol, or the activation of HO-1. This is believed to be the reason why chronic elevated levels of cholesterol might cause cardiovascular health issues.
Vitiligo
NRF2 overexpression has also been demonstrated to inhibit the capability to repigment in vitiligo as it might obstruct Tyrosinase, or TYR, action which is essential for repigmentation through melaninogenesis. Research studies have demonstrated that this process may be one of the primary reasons as to why people with vitiligo don’t seem to activate Nrf2 as efficiently as people without vitiligo.
Why NRF2 May Not Function Properly
Hormesis
NRF2 has to be hormetically activated in order to be able to take advantage of its benefits. In other words, Nrf2 shouldn’t trigger every minute or every day,�therefore, it’s a great idea to take breaks from it, by way of instance, 5 days on 5 days off or every other day. NRF2 must also accomplish a specific threshold to trigger its hormetic response, where a small stressor may not be enough to trigger it.
DJ-1 Oxidation
Protein deglycase DJ-1, or just DJ-1, also called the Parkinson’s disease protein, or PARK7, is a master regulator and detector of the redox status in the human body. DJ-1 is essential towards regulating how long NRF2 can perform its function and produce an antioxidant response. In the case that DJ-1 becomes overoxidized, the cells will make the DJ-1 protein less accessible.
This process induces NRF2 activation to expire too fast since DJ-1 is paramount for maintaining balanced levels of NRF2 and preventing them from being broken down in the cell. In case the DJ-1 protein is non-existent or overoxidized, NRF2 expression will probably be minimal, even using DIM or alternative NRF2 activators. DJ-1 expression is imperative to restore impaired NRF2 action.
Chronic Illness
If you have a chronic illness, including CIRS, chronic infections/dysbiosis/SIBO, or heavy metal build up, such as mercury and/or that from root canals, these can obstruct the systems of NRF2 and phase two detoxification. Rather than oxidative stress turning NRF2 into an antioxidant, NRF2 will not trigger and oxidative stress can remain in the cell and cause damage, meaning, there is no antioxidant response. This is a significant reason why many people with CIRS have several sensitivities and reach to numerous factors. Some people believe they may be�having a herx response, however, this reaction may only be damaging the cells farther.
Treating chronic illness, however, will permit the liver to discharge toxins into the bile, gradually developing the hormetic response of NRF2 activation. If the bile remains toxic and it’s not excreted from the human body, it will reactivate NRF2’s oxidative stress and cause you to feel worse once it’s reabsorbed from the gastrointestinal, or GI, tract. For example, ochratoxin A may block NRF2. Aside from treating the problem, histone deacetylase inhibitors can block the oxidative reaction from a number of the factors which trigger NRF2 activation but it might also prevent NRF2 from triggerring�normally, which might ultimately fail to serve its purpose.
Fish Oil Dysregulation
Cholinergics are substances which boost acetylcholine, or ACh, and choline in the brain through the increase of ACh, particularly when inhibiting the breakdown of ACh. Patients with CIRS often have problems with the dysregulation of acetylcholine levels in the human body, especially in the brain. Fish oil triggers NRF2, activating its protective antioxidant mechanism within the cells.
People with chronic illnesses might have problems with cognitive stress and acetylcholine excitotoxicity, from organophosphate accumulation, which might cause fish oil to create�inflammation within the human body. Choline deficiency additionally induces NRF2 activation. Including choline into your diet, (polyphenols, eggs, etc.) can help enhance the effects of cholinergic dysregulation.
What Decreases NRF2?
Decreasing NRF2 overexpression is best for people that have cancer, although it may be beneficial for a variety of other health issues.
Diet, Supplements, and Common Medicines:
Apigenin (higher doses)
Brucea javanica
Chestnuts
EGCG (high doses increase NRF2)
Fenugreek (Trigonelline)
Hiba (Hinokitiol / ?-thujaplicin)
High Salt Diet
Luteolin (Celery, green pepper, parsley, perilla leaf, and chamomile tea – higher doses may increase NRF2 – 40 mg/kg luteolin three times per week )
Metformin (chronic intake)
N-Acetyl-L-Cysteine (NAC, by blocking the oxidative response, esp at high doses)
Orange Peel (have polymethoxylated flavonoids)
Quercetin (higher doses may increase NRF2 – 50 mg/kg/d quercetin)
Salinomycin (drug)
Retinol (all-trans retinoic acid)
Vitamin C when combined with Quercetin
Zi Cao (Purple Gromwel has Shikonin/Alkannin)
Pathways and Other:
Bach1
BET
Biofilms
Brusatol
Camptothecin
DNMT
DPP-23
EZH2
Glucocorticoid Receptor signaling (Dexamethasone and Betamethasone as well)
GSK-3? (regulatory feedback)
HDAC activation?
Halofuginone
Homocysteine (ALCAR can reverse this homocysteine induce low levels of NRF2)
IL-24
Keap1
MDA-7
NF?B
Ochratoxin A(aspergillus and pencicllium species)
Promyelocytic leukemia protein
p38
p53
p97
Retinoic acid receptor alpha
Selenite
SYVN1 (Hrd1)
STAT3 inhibition (such as Cryptotanshinone)
Testosterone (and Testosterone propionate, although TP intranasally may increase NRF2)
Trecator (Ethionamide)
Trx1 (via reduction of Cys151 in Keap1 or of Cys506 in the NLS region of Nrf2)
Trolox
Vorinostat
Zinc Deficiency (makes it worse in the brain)
Nrf2 Mechanism Of Action
Oxidative stress triggers through CUL3 where NRF2 from KEAP1, a negative inhibitor, subsequently enters the nucleus of these cells, stimulating the transcription of the AREs, turning sulfides into disulfides, and turning them into more antioxidant genes, leading to the upregulation of antioxidants, such as GSH, GPX, GST, SOD, etc.. The rest of these can be seen in the list below:
Increases AKR
Increases ARE
Increases ATF4
Increases Bcl-xL
Increases Bcl-2
Increases BDNF
Increases BRCA1
Increases c-Jun
Increases CAT
Increases cGMP
Increases CKIP-1
Increases CYP450
Increases Cul3
Increases GCL
Increases GCLC
Increases GCLM
Increases GCS
Increases GPx
Increases GR
Increases GSH
Increases GST
Increases HIF1
Increases HO-1
Increases HQO1
Increases HSP70
Increases IL-4
Increases IL-5
Increases IL-10
Increases IL-13
Increases K6
Increases K16
Increases K17
Increases mEH
Increases Mrp2-5
Increases NADPH
Increases Notch 1
Increases NQO1
Increases PPAR-alpha
Increases Prx
Increases p62
Increases Sesn2
Increases Slco1b2
Increases sMafs
Increases SOD
Increases Trx
Increases Txn(d)
Increases UGT1(A1/6)
Increases VEGF
Reduces ADAMTS(4/5)
Reduces alpha-SMA
Reduces ALT
Reduces AP1
Reduces AST
Reduces Bach1
Reduces COX-2
Reduces DNMT
Reduces FASN
Reduces FGF
Reduces HDAC
Reduces IFN-?
Reduces IgE
Reduces IGF-1
Reduces IL-1b
Reduces IL-2
Reduces IL-6
Reduces IL-8
Reduces IL-25
Reduces IL-33
Reduces iNOS
Reduces LT
Reduces Keap1
Reduces MCP-1
Reduces MIP-2
Reduces MMP-1
Reduces MMP-2
Reduces MMP-3
Reduces MMP-9
Reduces MMP-13
Reduces NfkB
Reduces NO
Reduces SIRT1
Reduces TGF-b1
Reduces TNF-alpha
Reduces Tyr
Reduces VCAM-1
Encoded from the NFE2L2 gene, NRF2, or nuclear erythroid 2-related factor 2, is a transcription factor in the basic leucine zipper, or bZIP, superfamily which utilizes a Cap’n’Collar, or CNC structure.
It promotes nitric enzymes, biotransformation enzymes, and xenobiotic efflux transporters.
It is an essential regulator at the induction of the phase II antioxidant and detoxification enzyme genes, which protect cells from damage caused by oxidative�stress and electrophilic attacks.
During homeostatic conditions, Nrf2 is sequestered in the cytosol through bodily attachment of the N-terminal domain of Nrf2, or the Kelch-like ECH-associated protein or Keap1, also referred to as INrf2 or Inhibitor of Nrf2, inhibiting Nrf2 activation.
It may also be controlled by mammalian selenoprotein thioredoxin reductase 1, or TrxR1, which functions as a negative regulator.
Upon vulnerability to electrophilic stressors, Nrf2 dissociates from Keap1, translocating into the nucleus, where it then heterodimerizes with a range of transcriptional regulatory protein.
Frequent interactions comprise with those of transcription authorities Jun and Fos, which can be members of the activator protein family of transcription factors.
After dimerization, these complexes then bind to antioxidant/electrophile responsive components ARE/EpRE and activate transcription, as is true with the Jun-Nrf2 complex, or suppress transcription, much like the Fos-Nrf2 complex.
The positioning of the ARE, which is triggered or inhibited, will determine which genes are transcriptionally controlled by these variables.
When ARE is triggered:
Activation of the�synthesis of antioxidants is capable of detoxifying ROS like catalase, superoxide-dismutase, or SOD, GSH-peroxidases, GSH-reductase, GSH-transferase, NADPH-quinone oxidoreductase, or NQO1, Cytochrome P450 monooxygenase system, thioredoxin, thioredoxin reductase, and HSP70.
Activation of this GSH synthase permits a noticeable growth of the�GSH intracellular degree, which is quite protective.
The augmentation of this synthesis and degrees of phase II enzymes like UDP-glucuronosyltransferase, N-acetyltransferases, and sulfotransferases.
The upregulation of HO-1, which is a really protective receptor with a potential growth of CO that in conjunction with NO allows vasodilation of ischemic cells.
Reduction of iron overload through elevated ferritin and bilirubin as a lipophilic antioxidant. Both the phase II proteins along with the antioxidants are able to fix the chronic oxidative stress and also to revive a normal redox system.
GSK3? under the management of AKT and PI3K, phosphorylates Fyn resulting in Fyn nuclear localization, which Fyn phosphorylates Nrf2Y568 leading to nuclear export and degradation of Nrf2.
NRF2 also dampens the TH1/TH17 response and enriches the TH2 response.
HDAC inhibitors triggered the Nrf2 signaling pathway and up-regulated that the Nrf2 downstream targets HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit, or GCLC, by curbing Keap1 and encouraging dissociation of Keap1 from Nrf2, Nrf2 nuclear translocation, and Nrf2-ARE binding.
Nrf2 includes a half-life of about 20 minutes under basal conditions.
Diminishing the IKK? pool through Keap1 binding reduces I?B? degradation and might be the elusive mechanism by which Nrf2 activation is proven to inhibit NF?B activation.
Keap1 does not always have to be downregulated to get NRF2 to operate, such as chlorophyllin, blueberry, ellagic acid, astaxanthin, and tea polyphenols may boost NRF2 and KEAP1 at 400 percent.
Nrf2 regulates negatively through the term of stearoyl CoA desaturase, or SCD, and citrate lyase, or CL.
Genetics
KEAP1
rs1048290
C allele – showed a significant risk for and a protective effect against drug resistant epilepsy (DRE)
rs11085735 (I’m AC)
associated with rate of decline of lung function in the LHS
MAPT
rs242561
T allele – protective allele for Parkinsonian disorders – had stronger NRF2/sMAF binding and was associated with the higher MAPT mRNA levels in 3 different regions in brain, including cerebellar cortex (CRBL), temporal cortex (TCTX), intralobular white matter (WHMT)
NFE2L2 (NRF2)
rs10183914 (I’m CT)
T allele – increased levels of Nrf2 protein and delayed age of onset of Parkinson’s by four years
rs16865105 (I’m AC)
C allele – had higher risk of Parkinson’s Disease
rs1806649 (I’m CT)
C allele – has been identified and may be relevant for breast cancer etiology.
associated with increased risk of hospital admissions during periods of high PM10 levels
rs1962142 (I’m GG)
T allele – was associated with a low level of cytoplasmic NRF2 expression (P = 0.036) and negative sulfiredoxin expression (P = 0.042)
A allele – protected from forearm blood flow (FEV) decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
rs2001350 (I’m TT)
T allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
rs2364722 (I’m AA)
A allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
rs2364723
C allele – associated with significantly reduced FEV in Japanese smokers with lung cancer
rs2706110
G allele – showed a significant risk for and a protective effect against drug resistant epilepsy (DRE)
AA alleles – showed significantly reduced KEAP1 expression
AA alleles – was associated with an increased risk of breast cancer (P = 0.011)
rs2886161 (I’m TT)
T allele – associated with Parkinson’s Disease
rs2886162
A allele – was associated with low NRF2 expression (P = 0.011; OR, 1.988; CI, 1.162�3.400) and the AA genotype was associated with a worse survival (P = 0.032; HR, 1.687; CI, 1.047�2.748)
rs35652124 (I’m TT)
A allele – associated with higher associated with age at onset for Parkinson’s Disease vs G allele
C allele – had increase NRF2 protein
T allele – had less NRF2 protein and greater risk of heart disease and blood pressure
rs6706649 (I’m CC)
C allele – had lower NRF2 protein and increase risk for Parkinson’s Disease
rs6721961 (I’m GG)
T allele – had lower NRF2 protein
TT alleles – association between cigarette smoking in heavy smokers and a decrease in semen quality
TT allele – was associated with increased risk of breast cancer [P = 0.008; OR, 4.656; confidence interval (CI), 1.350�16.063] and the T allele was associated with a low extent of NRF2 protein expression (P = 0.0003; OR, 2.420; CI, 1.491�3.926) and negative SRXN1 expression (P = 0.047; OR, 1.867; CI = 1.002�3.478)
T allele – allele was also nominally associated with ALI-related 28-day mortality following systemic inflammatory response syndrome
T allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
G allele – associated with increased risk of ALI following major trauma in European and African-Americans (odds ratio, OR 6.44; 95% confidence interval
AA alleles – associated with infection-induced asthma
AA alleles – exhibited significantly diminished NRF2 gene expression and, consequently, an increased risk of lung cancer, especially those who had ever smoked
AA alleles – had a significantly higher risk for developing T2DM (OR 1.77; 95% CI 1.26, 2.49; p = 0.011) relative to those with the CC genotype
AA alleles – strong association between wound repair and late toxicities of radiation (associated with a significantly higher risk for developing late effects in African-Americans with a trend in Caucasians)
associated with oral estrogen therapy and risk of venous thromboembolism in postmenopausal women
rs6726395 (I’m AG)
A allele – protected from FEV1 decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
A allele – associated with significantly reduced FEV1 in Japanese smokers with lung cancer
GG alleles – had higher NRF2 levels and decreased risk of macular degeneration
GG alleles – had higher survival with Cholangiocarcinoma
rs7557529 (I’m CT)
C allele – associated with Parkinson’s Disease
Oxidative stress and other stressors can cause cell damage which may eventually lead to a variety of health issues. Research studies have demonstrated that Nrf2 activation can promote the human body’s protective antioxidant mechanism, however, researchers have discussed that Nrf2 overexpression can have tremendous risks towards overall health and wellness. Various types of cancer can also occur with Nrf2 overactivation.
Dr. Alex Jimenez D.C., C.C.S.T. Insight
Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More
Isothiocyanates are some of the most important plant compounds you can get in your diet. In this video I make the most comprehensive case for them that has ever been made. Short attention span? Skip to your favorite topic by clicking one of the time points below. Full timeline below.
Key sections:
00:01:14 – Cancer and mortality
00:19:04 – Aging
00:26:30 – Brain and behavior
00:38:06 – Final recap
00:40:27 – Dose
Full timeline:
00:00:34 – Introduction of sulforaphane, a major focus of the video.
00:01:14 – Cruciferous vegetable consumption and reductions in all-cause mortality.
00:02:12 – Prostate cancer risk.
00:02:23 – Bladder cancer risk.
00:02:34 – Lung cancer in smokers risk.
00:02:48 – Breast cancer risk.
00:03:13 – Hypothetical: what if you already have cancer? (interventional)
00:03:35 – Plausible mechanism driving the cancer and mortality associative data.
00:04:38 – Sulforaphane and cancer.
00:05:32 – Animal evidence showing strong effect of broccoli sprout extract on bladder tumor development in rats.
00:06:06 – Effect of direct supplementation of sulforaphane in prostate cancer patients.
00:07:09 – Bioaccumulation of isothiocyanate metabolites in actual breast tissue.
00:08:32 – Inhibition of breast cancer stem cells.
00:08:53 – History lesson: brassicas were established as having health properties even in ancient Rome.
00:09:16 – Sulforaphane’s ability to enhance carcinogen excretion (benzene, acrolein).
00:09:51 – NRF2 as a genetic switch via antioxidant response elements.
00:10:10 – How NRF2 activation enhances carcinogen excretion via glutathione-S-conjugates.
00:10:34 – Brussels sprouts increase glutathione-S-transferase and reduce DNA damage.
00:11:20 – Broccoli sprout drink increases benzene excretion by 61%.
00:13:31 – Broccoli sprout homogenate increases antioxidant enzymes in the upper airway.
00:15:45 – Cruciferous vegetable consumption and heart disease mortality.
00:16:55 – Broccoli sprout powder improves blood lipids and overall heart disease risk in type 2 diabetics.
00:19:04 – Beginning of aging section.
00:19:21 – Sulforaphane-enriched diet enhances lifespan of beetles from 15 to 30% (in certain conditions).
00:20:34 – Importance of low inflammation for longevity.
00:22:05 – Cruciferous vegetables and broccoli sprout powder seem to reduce a wide variety of inflammatory markers in humans.
00:36:32 – Sulforaphane improves learning in model of type II diabetes in mice.
00:37:19 – Sulforaphane and duchenne muscular dystrophy.
00:37:44 – Myostatin inhibition in muscle satellite cells (in vitro).
00:38:06 – Late-video recap: mortality and cancer, DNA damage, oxidative stress and inflammation, benzene excretion, cardiovascular disease, type II diabetes, effects on the brain (depression, autism, schizophrenia, neurodegeneration), NRF2 pathway.
00:40:27 – Thoughts on figuring out a dose of broccoli sprouts or sulforaphane.
00:41:01 – Anecdotes on sprouting at home.
00:43:14 – On cooking temperatures and sulforaphane activity.
00:43:45 – Gut bacteria conversion of sulforaphane from glucoraphanin.
00:44:24 – Supplements work better when combined with active myrosinase from vegetables.
00:44:56 – Cooking techniques and cruciferous vegetables.
00:46:06 – Isothiocyanates as goitrogens.
According to research studies, Nrf2, is a fundamental transcription factor which activates the cells’ protective antioxidant mechanisms to detoxify the human body. The overexpression of Nrf2, however, can cause health issues. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion:�Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.
Many current research studies on cancer have allowed health professionals to understand the way the body detoxes. By analyzing upregulated genes in tumorous cells, researchers discovered the nuclear erythroid 2-related factor 2 signaling pathway, best known as Nrf2. NRF2 is an important transcription factor which activates the human body’s protective antioxidant mechanisms in order to regulate oxidation from both external and internal factors to prevent increased levels of oxidative stress.
Principles of Nrf2
NRF2 is essential towards maintaining overall health and wellness because it�serves the primary purpose of regulating how we manage everything we’re exposed to on a daily basis and not become sick. NRF2 activation plays a role in the phase II detoxification system.�Phase II detoxification takes lipophilic, or�fat soluble, free radicals and converts them into hydrophilic, or water soluble,�substances for excretion while inactivating exceptionally reactive metabolites and chemicals as a consequence of phase I.
NRF2 activation reduces overall oxidation and inflammation of the human body through a hormetic effect. To trigger NRF2, an inflammatory reaction due to oxidation must occur in order for the cells to produce an adaptive response and create antioxidants, such as glutathione. To break down the principle of Nrf2, essentially, oxidative stress activates NRF2 which then activates an antioxidant response in the human body. NRF2 functions to balance redox signaling, or the equilibrium of oxidant and antioxidant levels in the cell.
A great illustration of how this process functions can be demonstrated with exercise. Through every workout, the muscle adapts so that it can accommodate another workout session. If NRF2 becomes under- or over-expressed due to chronic infections or increased exposure to toxins, which may be observed in patients who have chronic inflammatory response syndrome, or CIRS, the health issues may worsen�following NRF2 activation. Above all, if DJ-1 becomes over-oxidized, NRF2 activation will end�too quickly.
Effects of NRF2 Activation
NRF2 activation is highly expressed in the lungs, liver, and kidneys. Nuclear erythroid 2-related factor 2, or NRF2, most commonly functions by counteracting increased levels of oxidation in the human body which can lead to oxidative stress. Nrf2 activation can help treat a variety of health issues, however, over-activation of Nrf2 may worsen various problems, which are demonstrated below.
Periodic activation of Nrf2 can help:
Aging (ie Longevity)
Autoimmunity and Overall Inflammation (ie Arthritis, Autism)
Cancer and Chemoprotection (ie EMF Exposure)
Depression and Anxiety (ie PTSD)
Drug Exposure (Alcohol, NSAIDs )
Exercise and Endurance Performance
Gut Disease (ie SIBO, Dysbiosis, Ulcerative Colitis)
Cancer (ie Brain, Breast, Head, Neck Pancreatic, Prostate, Liver, Thyroid)
Chronic Inflammatory Response Syndrome (CIRS)
Heart Transplant (while open NRF2 may be bad, NRF2 can help with repair)
Hepatitis C
Nephritis (severe cases)
Vitiligo
Furthermore, NRF2 can help make specific nutritional supplements, drugs,�and medications work. Many natural�supplements can also help trigger NRF2. Through current research studies, researchers have demonstrated that a large number of compounds which were once believed to be antioxidants were really pro-oxidants. That’s because nearly all of them need NRF2 to function, even supplements like curcumin and fish oil. Cocoa, for example, was shown to generate antioxidant effects in mice which possess the NRF2 gene.
Ways To Activate NRF2
In the case of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, stroke or even autoimmune diseases, it’s probably best to have Nrf2 upregulated, but in a hormetic fashion. Mixing NRF2 activators may also have an additive or synergistic effect, as occasionally it can be dose-dependent. The top ways to increase Nrf2 expression are listed below:
HIST (Exercise) + CoQ10 + Sun (these synergize very well)
Broccoli Sprouts + LLLT on my head and gut
Butyrate + Super Coffee + Morning Sun
Acupuncture (this is an alternative method, laser acupuncture may also be used)
Fasting
Cannabidiol (CBD)
Lion’s Mane + Melatonin
Alpha-lipoic acid + DIM
Wormwood
PPAR-gamma Activation
The following comprehensive listing containing over 350 other ways to activate Nrf2 through diet, lifestyle and devices, probiotics, supplements, herbs and oils, hormones and neurotransmitters, drugs/medications and chemicals, pathways/transcription factors, as well as other ways, is only a brief guide as to what can trigger Nrf2. For the sake of brevity in this article, we have left out over 500 other foods, nutritional supplements and compounds which can help activate Nrf2. The following are listed below:
Diet:
Acai Berries
Alcohol (Red wine is better, especially if there is a cork in it, as protocatechuic aldehyde from corks can also activate NRF2. In general, alcohol is not recommended, although acute intake increases NRF2. Chronic intake may decrease NRF2.
Algae (kelp)
Apples
Black Tea
Brazil Nuts
Broccoli Sprouts (and other isothiocyanates, sulforaphane as well as cruciferous vegetables like bok choy that have D3T)
Blueberries (0.6-10 g/day)
Carrots (falcarinone)
Cayenne Pepper (Capsaicin)
Celery (Butylphthalide)
Chaga (Betulin)
Chamomile Tea
Chia
Chinese Potato
Chokeberries (Aronia)
Chocolate (Dark or Cocoa)
Cinnamon
Coffee (such as chlorogenic acid, Cafestol and Kahweol)
Cordyceps
Fish (and Shellfish)
Flaxseed
Garlic
Ghee (possibly)
Ginger (and Cardamonin)
Gojiberries
Grapefruit (Naringenin – 50 mg/kg/d naringenin)
Grapes
Green Tea
Guava
Heart Of Palm
Hijiki/Wakame
Honeycomb
Kiwi
Legumes
Lion’s Mane
Mahuwa
Mangos (Mangiferin)
Mangosteen
Milk (goat, cow – via regulation of microbiome)
Mulberries
Olive Oil (pomace – hydroxytyrosol and Oleanolic Acid)
Omega 6 Fatty Acids (Lipoxin A4)
Osange Oranges (Morin)
Oyster Mushrooms
Papaya
Peanuts
Pigeon Peas
Pomegranate (Punicalagin, Ellagic Acid)
Propolis (Pinocembrin)
Purple Sweet Potatoes
Rambutan (Geraniin)
Onions
Reishi
Rhodiola Rosea (Salidroside)
Rice Bran (cycloartenyl ferulate)
Riceberry
Rooibos Tea
Rosemary
Sage
Safflower
Sesame Oil
Soy (and isoflavones, Daidzein, Genistein)
Squash
Strawberries
Tartary Buckwheat
Thyme
Tomatoes
Tonka Beans
Turmeric
Wasabi
Watermelon
Lifestyle and Devices:
Acupuncture and Electroacupuncture (via collagen cascade on ECM)
Exercise (Acute exercise like HIST or HIIT seems to be more beneficial for inducing NRF2, while longer exercise doesn�t induce NRF2, but does increase glutathione levels)
High Fat Diet (diet)
High Heat (Sauna)
Hydrogen Inhalation and Hydrogen Water
Hyperbaric Oxygen Therapy
Infrared Therapy (such as Joovv)
Intravenous Vitamin C
Ketogenic Diet
Ozone
Smoking (not recommended – acutely smoking increase NRF2, chronically smoking decreases NRF2. If you choose to smoke, Holy Basil may help protect against downregulation of NRF2)
Sun (UVB and Infrared)
Probiotics:
Bacillus subtilis (fmbJ)
Clostridium butyricum (MIYAIRI 588)
Lactobacillus brevis
Lactobacillus casei (SC4 and 114001)
Lactobacillus collinoides
Lactobacillus gasseri (OLL2809, L13-Ia, and SBT2055)
Lactobacillus helveticus (NS8)
Lactobacillus paracasei (NTU 101)
Lactobacillus plantarum (C88, CAI6, FC225, SC4)
Lactobacillus rhamnosus (GG)
Supplements, Herbs, and Oils:
Acetyl-L-Carnitine (ALCAR) and Carnitine
Allicin
Alpha-lipoic acid
Amentoflavone
Andrographis paniculata
Agmatine
Apigenin
Arginine
Artichoke (Cyanropicrin)
Ashwaganda
Astragalus
Bacopa
Beefsteak (Isogemaketone)
Berberine
Beta-caryophyllene
Bidens Pilosa
Black Cumin Seed Oil (Thymoquinone)
Boswellia
Butein
Butyrate
Cannabidiol (CBD)
Carotenioids (like Beta-carotene [synergy with Lycopene – 2 � 15 mg/d lycopene], Fucoxanthin, Zeaxanthin, Astaxanthin, and Lutein)
Chitrak
Chlorella
Chlorophyll
Chrysanthemum zawadskii
Cinnamomea
Common Sundew
Copper
Coptis
CoQ10
Curcumin
Damiana
Dan Shen/Red Sage (Miltirone)
DIM
Dioscin
Dong Ling Cao
Dong Quai (female ginseng)
Ecklonia Cava
EGCG
Elecampane / Inula
Eucommia Bark
Ferulic Acid
Fisetin
Fish Oil (DHA/EPA – 3 � 1 g/d fish oil containing 1098 mg EPA and 549 mg DHA)
Galangal
Gastrodin (Tian Ma)
Gentiana
Geranium
Ginkgo Biloba (Ginkgolide B)
Glasswort
Gotu Kola
Grape Seed Extract
Hairy Agrimony
Haritaki (Triphala)
Hawthorn
Helichrysum
Henna (Juglone)
Hibiscus
Higenamine
Holy Basil/Tulsi (Ursolic Acid)
Hops
Horny Goat Weed (Icariin/Icariside)
Indigo Naturalis
Iron (not recommended unless essential)
I3C
Job’s Tears
Moringa Oleifera (such as Kaempferol)
Inchinkoto (combo of Zhi Zi and Wormwood)
Kudzu Root
Licorice Root
Lindera Root
Luteolin (high doses for activation, lower doses inhibit NRF2 in cancer though)
Magnolia
Manjistha
Maximowiczianum (Acerogenin A)
Mexican Arnica
Milk Thistle
MitoQ
Mu Xiang
Mucuna Pruriens
Nicotinamide and NAD+
Panax Ginseng
Passionflower (such as Chrysin, but chyrisin may also reduce NRF2 via dysregulation of PI3K/Akt signaling)
Resveratrol (Piceid and other phytoestrogens essentially, Knotweed)
Rose Hips
Rosewood
Rutin
Sappanwood
Sarsaparilla
Saururus chinensis
SC-E1 (Gypsum, Jasmine, Licorice, Kudzu, and Balloon Flower)
Schisandra
Self Heal (prunella)
Skullcap (Baicalin and Wogonin)
Sheep Sorrel
Si Wu Tang
Sideritis
Spikenard (Aralia)
Spirulina
St. John’s Wort
Sulforaphane
Sutherlandia
Tao Hong Si Wu
Taurine
Thunder God Vine (Triptolide)
Tocopherols (such as Vitamin E or Linalool)
Tribulus R
Tu Si Zi
TUDCA
Vitamin A (although other retinoids inhibit NRF2)
Vitamin C (high dose only, low dose does inhibit�NRF2)
Vitex/Chaste Tree
White Peony (Paeoniflorin from Paeonia lactiflora)
Wormwood (Hispidulin and Artemisinin)
Xiao Yao Wan (Free and Easy Wanderer)
Yerba Santa (Eriodictyol)
Yuan Zhi (Tenuigenin)
Zi Cao (will reduce NRF2 in cancer)
Zinc
Ziziphus Jujube
Hormones and Neurotransmitters:
Adiponectin
Adropin
Estrogen (but may decrease NRF2 in breast tissue)
Melatonin
Progesterone
Quinolinic Acid (in protective response to prevent excitotoxicity)
Serotonin
Thyroid Hormones like T3 (can increase NRF2 in healthy cells, but decrease it in cancer)
Vitamin D
Drugs/Medications and Chemicals:
Acetaminophen
Acetazolamide
Amlodipine
Auranofin
Bardoxolone methyl (BARD)
Benznidazole
BHA
CDDO-imidazolide
Ceftriaxone (and beta-lactam antibiotics)
Cialis
Dexamethasone
Diprivan (Propofol)
Eriodictyol
Exendin-4
Ezetimibe
Fluoride
Fumarate
HNE (oxidized)
Idazoxan
Inorganic arsenic and sodium arsenite
JQ1 (may inhibit NRF2 as well, unknown)
Letairis
Melphalan
Methazolamide
Methylene Blue
Nifedipine
NSAIDs
Oltipraz
PPIs (such as Omeprazole and Lansoprazole)
Protandim – great results in vivo, but weak/non-existent at activating NRF2 in humans
Probucol
Rapamycin
Reserpine
Ruthenium
Sitaxentan
Statins (such as Lipitor and Simvastatin)
Tamoxifen
Tang Luo Ning
tBHQ
Tecfidera (Dimethyl fumarate)
THC (not as strong as CBD)
Theophylline
Umbelliferone
Ursodeoxycholic Acid (UDCA)
Verapamil
Viagra
4-Acetoxyphenol
Pathways/Transcription Factors:
?7 nAChR activation
AMPK
Bilirubin
CDK20
CKIP-1
CYP2E1
EAATs
Gankyrin
Gremlin
GJA1
H-ferritin ferroxidase
HDAC inhibitors (such as valproic acid and TSA, but can cause NRF2 instability)
Heat Shock Proteins
IL-17
IL-22
Klotho
let-7 (knocks down mBach1 RNA)
MAPK
Michael acceptors (most)
miR-141
miR-153
miR-155 (knocks down mBach1 RNA as well)
miR-7 (in brain, helps with cancer and schizophrenia)
Notch1
Oxidatives stress (such as ROS, RNS, H2O2) and Electrophiles
PGC-1?
PKC-delta
PPAR-gamma (synergistic effects)
Sigma-1 receptor inhibition
SIRT1 (increases NRF2 in the brain and lungs but may decrease it overall)
SIRT2
SIRT6 (in the liver and brain)
SRXN1
TrxR1 inhibition (attenuation or depletion as well)
Zinc protoporphyrin
4-HHE
Other:
Ankaflavin
Asbestos
Avicins
Bacillus amyloliquefaciens (used in agriculture)
Carbon Monoxide
Daphnetin
Glutathione Depletion (depletion of 80%�90% possibly)
Gymnaster koraiensis
Hepatitis C
Herpes (HSV)
Indian ash tree
Indigowoad Root
Isosalipurposide
Isorhamentin
Monascin
Omaveloxolone (strong, aka RTA-408)
PDTC
Selenium Deficiency (selenium deficiency can increase NRF2)
Siberian Larch
Sophoraflavanone G
Tadehagi triquetrum
Toona sinensis (7-DGD)
Trumpet Flower
63171 and 63179 (strong)
The nuclear erythroid 2-related factor 2 signaling pathway, best known by the acronym Nrf2, is a transcription factor which plays the major role of regulating the protective antioxidant mechanisms of the human body, particularly in order to control oxidative stress. While increased levels of oxidative stress can activate Nrf2, its effects are tremendously enhanced through the presence of specific compounds. Certain foods and supplements help activate Nrf2 in the human body, including the isothiocyanate sulforaphane from broccoli sprouts. Dr. Alex Jimenez D.C., C.C.S.T. Insight
Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More
Isothiocyanates are some of the most important plant compounds you can get in your diet. In this video I make the most comprehensive case for them that has ever been made. Short attention span? Skip to your favorite topic by clicking one of the time points below. Full timeline below.
Key sections:
00:01:14 – Cancer and mortality
00:19:04 – Aging
00:26:30 – Brain and behavior
00:38:06 – Final recap
00:40:27 – Dose
Full timeline:
00:00:34 – Introduction of sulforaphane, a major focus of the video.
00:01:14 – Cruciferous vegetable consumption and reductions in all-cause mortality.
00:02:12 – Prostate cancer risk.
00:02:23 – Bladder cancer risk.
00:02:34 – Lung cancer in smokers risk.
00:02:48 – Breast cancer risk.
00:03:13 – Hypothetical: what if you already have cancer? (interventional)
00:03:35 – Plausible mechanism driving the cancer and mortality associative data.
00:04:38 – Sulforaphane and cancer.
00:05:32 – Animal evidence showing strong effect of broccoli sprout extract on bladder tumor development in rats.
00:06:06 – Effect of direct supplementation of sulforaphane in prostate cancer patients.
00:07:09 – Bioaccumulation of isothiocyanate metabolites in actual breast tissue.
00:08:32 – Inhibition of breast cancer stem cells.
00:08:53 – History lesson: brassicas were established as having health properties even in ancient Rome.
00:09:16 – Sulforaphane’s ability to enhance carcinogen excretion (benzene, acrolein).
00:09:51 – NRF2 as a genetic switch via antioxidant response elements.
00:10:10 – How NRF2 activation enhances carcinogen excretion via glutathione-S-conjugates.
00:10:34 – Brussels sprouts increase glutathione-S-transferase and reduce DNA damage.
00:11:20 – Broccoli sprout drink increases benzene excretion by 61%.
00:13:31 – Broccoli sprout homogenate increases antioxidant enzymes in the upper airway.
00:15:45 – Cruciferous vegetable consumption and heart disease mortality.
00:16:55 – Broccoli sprout powder improves blood lipids and overall heart disease risk in type 2 diabetics.
00:19:04 – Beginning of aging section.
00:19:21 – Sulforaphane-enriched diet enhances lifespan of beetles from 15 to 30% (in certain conditions).
00:20:34 – Importance of low inflammation for longevity.
00:22:05 – Cruciferous vegetables and broccoli sprout powder seem to reduce a wide variety of inflammatory markers in humans.
00:36:32 – Sulforaphane improves learning in model of type II diabetes in mice.
00:37:19 – Sulforaphane and duchenne muscular dystrophy.
00:37:44 – Myostatin inhibition in muscle satellite cells (in vitro).
00:38:06 – Late-video recap: mortality and cancer, DNA damage, oxidative stress and inflammation, benzene excretion, cardiovascular disease, type II diabetes, effects on the brain (depression, autism, schizophrenia, neurodegeneration), NRF2 pathway.
00:40:27 – Thoughts on figuring out a dose of broccoli sprouts or sulforaphane.
00:41:01 – Anecdotes on sprouting at home.
00:43:14 – On cooking temperatures and sulforaphane activity.
00:43:45 – Gut bacteria conversion of sulforaphane from glucoraphanin.
00:44:24 – Supplements work better when combined with active myrosinase from vegetables.
00:44:56 – Cooking techniques and cruciferous vegetables.
00:46:06 – Isothiocyanates as goitrogens.
According to many current research studies, the nuclear erythroid 2-related factor 2 signaling pathway, best known as Nrf2, is a fundamental transcription factor which activates the cells’ protective antioxidant mechanisms to detoxify the human body from both external and internal factors and prevent increased levels of oxidative stress. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion:�Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief. �
Oxidative stress is a major contributor in the development of a variety of health issues, including cancer, heart disease, diabetes, accelerated aging and neurodegeneration. Antioxidant rich foods, herbs and supplements can be utilized to protect the human body from high levels of oxidative stress. Recent research studies have demonstrated that the Nrf2 gene pathway can help amplify the effects of antioxidants. The benefits of Nrf2 are described below.
Protects the Body Against Toxins
NRF2 is an intrinsic substance which can protect the cells from harmful, internal and external compounds. NRF2 may help enrich the human body’s reaction to drugs/medications and toxins, improving the production of�proteins that help eliminate compounds from the cell, known as multidrug resistance-associated proteins, or MRPs.�By way of instance, NRF2 is triggered upon cigarette smoke inhalation to allow the lungs to detox.
Additionally, it is essential for the lungs to protect themselves against allergens, viral diseases, bacterial endotoxins, hyperoxia, and various environmental pollutants. The constant trigger of Nrf2 however, can decrease the levels of a substance known as glutathione throughout the human body. NRF2 may also protect the liver from toxicity and it can protect the liver from arsenic hepatotoxicity. Moreover, NRF2 protects the liver and brain from alcohol consumption. By way of instance, Nrf2 can protect�against acetaminophen toxicity.
Fights Inflammation And Oxidative Stress
NRF2 activation can help battle against inflammation by diminishing inflammatory cytokines, such as those present in psoriasis. NRF2 may also decrease inflammation associated with a variety of health issues like arthritis and fibrosis of the liver, kidney, and lungs. NRF2 may also help control allergies by lowering Th1/Th17 cytokines and raising TH2 cytokines. This can be beneficial for ailments like asthma.
NRF2 additionally protects against cellular damage from blue light�and from UVA/UVB� found in sunlight. Nrf2 deficiencies can make it a whole lot easier to get sunburnt. One rationale behind this is because NRF2 is capable of regulating collagen in response to UV radiation. Advanced Glycation End-Products, or AGEs, contribute to the development of many health issues, including diabetes and neurodegenerative diseases. NRF2 can decrease the oxidative stress of AGEs within the body. NRF2 may also protect the human body from higher levels of heat-based stress.
Enhances Mitochondria And Exercise Performance
NRF2 is a mitochondrial booster. NRF2 activation contributes to a rise in ATP energy for mitochondria, in addition to enhanced use of oxygen, or citrate, and fat. With no NRF2, mitochondria would just have the ability to function with sugar, or glucose, rather than fat. NRF2 is also essential for mitochondria to develop through a process known as biogenesis. NRF2 activation is vital in order to�take advantage of� the benefits of exercise.
Because of�Nrf2’s activity, exercise raises mitochondrial function, where this result may be amplified with CoQ10, Cordyceps, and Caloric Restriction. Moderate exercise or acute exercise induces mitochondrial biogenesis and an elevated synthesis of superoxide dismutase, or SOD, and heme-oxygenase-1, or HO-1, through NRF2 activation. Alpha-Lipoic Acid,�or ALA, and Dan Shen can boost NRF2 mediated mitochondrial biogenesis. Furthermore,�NRF2 can also improve exercise tolerance where NRF2 deletion makes exercise harmful.
Protects Against Hypoxia
NRF2 also helps protect the human body from cellular oxygen loss/depletion, a health issue called hypoxia. Individuals with CIRS have reduced levels of oxygen since their NRF2 is obstructed, resulting in reduced levels of both VEGF, HIF1, and HO-1. Ordinarily, in healthy individuals with hypoxia, miR-101, which is required for the creation of stem cells, are overexpressed and enhance amounts of NRF2/HO-1 and VEGF/eNOS, therefore preventing brain damage, but that does not appear to occur in CIRS.
Hypoxia, characterized by low HIF1, in CIRS can also result in a leaky blood brain barrier due to an NRF2 imbalance. Salidroside, located in the Rhodiola, functions on NRF2 activation and assists with hypoxia by increasing levels of VEGF and HIF1 within the human body. NRF2 can also ultimately protect against lactate buildup in the heart. NRF2 activation may also stop hypoxia-induced Altitude Motion Sickness, or AMS.
Slows Down Aging
Several compounds which may be fatal in massive quantities may increase longevity in rather tiny quantities due to xenohormesis through NRF2, PPAR-gamma, and FOXO. A�very small quantity of toxins raises the cell’s ability to become better equipped for the next time it’s challenged with a toxin, however, this is not an endorsement to consume poisonous�chemicals.
A good illustration of this process is with caloric restriction. NRF2 can improve the lifespan of cells by raising their levels of mitochondria and antioxidants as well as lowering the cells’ capability to die. NRF2 declines with aging because NRF2 prevents stem cells from dying and assists them to�regenerate. NRF2 plays a part in enhancing wound healing.
Boosts the Vascular System
Done correctly with the production of sulforaphane, NRF2 activation may protect against heart diseases like high blood pressure, or hypertension, and hardening of the arteries, or atherosclerosis. NRF2 can enhance Acetylcholine’s, or ACh, relaxing activity on the vascular system whilst reducing cholesterol-induced stress. Nrf2 activation may strengthen the heart, however, over-activated Nrf2 can raise the probability of cardiovascular disease.
Statins may prevent or lead to cardiovascular disease. NRF2 also plays a major part in balancing iron and calcium which may shield the human body from having elevated levels of iron. By way of instance, Sirtuin 2, or SIRT2, can regulate iron homeostasis in cells by activation of NRF2 which is believed to be required for healthy levels of iron. NRF2 can also help with Sickle Cell Disease, or SCD. NRF2 dysfunction might be a reason behind endotoxemia like with dysbiosis or lectins induced hypertension. Nrf2 may also protect the human body against amphetamine induced damage to the vascular system.
Fights Neuroinflammation
NRF2 can shield against and assist with inflammation of the brain, commonly referred to as neuroinflammation. Furthermore, NRF2 can help with an Assortment of Central Nervous System, or CNS, disorders, including:
Alzheimer’s Disease (AD) – reduces amyloid beta stress on mitochondria
Amyotrophic Lateral Sclerosis (ALS)
Huntington’s Disease (HD)
Multiple Sclerosis (MS)
Nerve Regeneration
Parkinson’s disease (PD) – protects dopamine
Spinal Cord Injury (SCI)
Stroke (ischemic and hemorrhagic) – aids hypoxia
Traumatic Brain Injury
NRF2 has revealed a decrease of neuroinflammation in teens with Autism Spectrum Disorders�or ASD. Idebenone pairs properly with NRF2 activators contrary to neuroinflammation. NRF2 may also improve the Blood Brain Barrier,�or BBB. By way of instance, NRF2 activation with carnosic acid obtained from rosemary and sage can cross the BBB and cause neurogenesis. NRF2 has also been demonstrated to raise�Brain Derived Neurotrophic Factor, or BDNF.
NRF2 also modulates some nutritional supplements capacity to cause Nerve Growth Factor, or NGF as it� can also aid with brain fog and glutamate-induced issues by modulating N-Methyl-D-Aspartate,�or NMDA receptors. It may also lower the oxidative stress from quinolinic acid, referred to as QUIN. NRF2 activation can protect against seizures and large doses can decrease the brink of a seizure. At regular doses of stimulation, NRF2 can enhance cognitive abilities following a seizure by lowering extracellular glutamate in the brain and by it’s ability to draw cysteine from glutamate and glutathione.
Relieves Depression
In depression, it’s normal to notice inflammation in the brain, especially from the prefrontal cortex and hippocampus, as well as decreased BDNF. In some versions of depression, NRF2 can improve depressive symptoms by lowering inflammation within the brain and increasing BDNF levels. Agmatine’s capability to decrease depression by raising noradrenaline, dopamine, serotonin, and BDNF in the hippocampus depends upon NRF2 activation.
Contains Anti-Cancer Properties
NRF2 is equally a tumor suppressor as it is a tumor promoter if not managed accordingly. NRF2 can protect against cancer caused by free radicals and oxidative stress, however, NRF2 overexpression can be found in cancer cells as well. Intense activation of NRF2 can assist with a variety of cancers. By way of instance, the supplement Protandim can reduce skin cancer by NRF2 activation.
Relieves Pain
Gulf War Illness, or GWI, a notable illness affecting Gulf War Veterans, is a collection of unexplained, chronic symptoms which may include tiredness, headaches, joint pain, indigestion, insomnia, dizziness, respiratory ailments, and memory issues. NRF2 can improve symptoms of GWI by diminishing hippocampal and general inflammation, in addition to decreasing pain. NRF2 can additionally assist with pain from bodily nerve injury and improve nerve damage from diabetic neuropathy.
Improves Diabetes
High glucose levels, best referred to as hyperglycemia, causes oxidative damage to the cells due to the disruption of mitochondrial function. NRF2 activation may shield the human body against hyperglycemia’s harm to the cell, thereby preventing cell death. NRF2 activation can additionally protect, restore, and enhance pancreatic beta-cell function, while reducing insulin resistance.
Protects Vision And Hearing
NRF2 can protect against harm to the eye from diabetic retinopathy. It might also avoid the formation of cataracts and protect photoreceptors contrary to light-induced death. NRF2 additionally shield the ear, or cochlea, from stress and hearing loss.
Might Help Obesity
NRF2 may help with obesity primarily due to its capacity to regulate variables that operate on fat accumulation in the human body. NRF2 activation with sulforaphane can raise inhibit of Fatty Acid Synthesis, or FAS, and Uncoupling Proteins, or UCP, resulting in less fat accumulation and more brown fat, characterized as fat which includes more mitochondria.
Protects The Gut
NRF2 helps protect the gut by safeguarding the intestine microbiome homeostasis. By way of instance, lactobacillus probiotics will trigger NRF2 to guard the gut from oxidative stress. NRF2 can also help prevent Ulcerative Colitis, or UC.
Protects Sex Organs
NRF2 can shield the testicles and keep sperm count from harm in people with diabetes. It can also assist with Erectile Dysfunction, or ED. Some libido boosting supplements like Mucuna, Tribulus, and Ashwaganda�may enhance�sexual function via NRF2 activation. Other factors that boost NRF2, such as sunlight or broccoli sprouts, can also help improve libido.
Regulates Bones And Muscles
Oxidative stress may result in bone density and strength reduction, which is normal in osteoporosis. NRF2 activation could have the ability to improve antioxidants in bones and protect against bone aging. NRF2 can also prevent muscle loss and enhance Duchenne Muscular Dystrophy, or DMD.
Contains Anti-Viral Properties
Last but not least, NRF2 activation can ultimately help defend the human body against several viruses. In patients with the dengue virus, symptoms were not as intense in individuals who had greater levels of NRF2 compared to individuals who had less degrees of NRF2. NRF2 can also help people who have Human Immunodeficiency-1 Virus,�or HIV. NRF2 can protect against the oxidative stress from Adeno-Associated Virus,�or AAV, and H. Pylori. Finally, Lindera Root may suppress Hepatitis C virus with NRF2 activation.
Nrf2, or NF-E2-related factor 2, is a transcription factor found in humans which regulates the expression of a specific set of antioxidant and detoxifying genes. This signaling pathway is activated due to oxidative stress as it enhances numerous antioxidant and phase II liver detoxification enzymes to restore homeostasis in the human body. Humans are adapted to function throughout a state of homeostasis or balance. When the body is confronted with oxidative stress, Nrf2 activates to regulate oxidation and control the stress it causes. Nrf2 is essential to prevent health issues associated with oxidative stress. Dr. Alex Jimenez D.C., C.C.S.T. Insight
Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More
Isothiocyanates are some of the most important plant compounds you can get in your diet. In this video I make the most comprehensive case for them that has ever been made. Short attention span? Skip to your favorite topic by clicking one of the time points below. Full timeline below.
Key sections:
00:01:14 – Cancer and mortality
00:19:04 – Aging
00:26:30 – Brain and behavior
00:38:06 – Final recap
00:40:27 – Dose
Full timeline:
00:00:34 – Introduction of sulforaphane, a major focus of the video.
00:01:14 – Cruciferous vegetable consumption and reductions in all-cause mortality.
00:02:12 – Prostate cancer risk.
00:02:23 – Bladder cancer risk.
00:02:34 – Lung cancer in smokers risk.
00:02:48 – Breast cancer risk.
00:03:13 – Hypothetical: what if you already have cancer? (interventional)
00:03:35 – Plausible mechanism driving the cancer and mortality associative data.
00:04:38 – Sulforaphane and cancer.
00:05:32 – Animal evidence showing strong effect of broccoli sprout extract on bladder tumor development in rats.
00:06:06 – Effect of direct supplementation of sulforaphane in prostate cancer patients.
00:07:09 – Bioaccumulation of isothiocyanate metabolites in actual breast tissue.
00:08:32 – Inhibition of breast cancer stem cells.
00:08:53 – History lesson: brassicas were established as having health properties even in ancient Rome.
00:09:16 – Sulforaphane’s ability to enhance carcinogen excretion (benzene, acrolein).
00:09:51 – NRF2 as a genetic switch via antioxidant response elements.
00:10:10 – How NRF2 activation enhances carcinogen excretion via glutathione-S-conjugates.
00:10:34 – Brussels sprouts increase glutathione-S-transferase and reduce DNA damage.
00:11:20 – Broccoli sprout drink increases benzene excretion by 61%.
00:13:31 – Broccoli sprout homogenate increases antioxidant enzymes in the upper airway.
00:15:45 – Cruciferous vegetable consumption and heart disease mortality.
00:16:55 – Broccoli sprout powder improves blood lipids and overall heart disease risk in type 2 diabetics.
00:19:04 – Beginning of aging section.
00:19:21 – Sulforaphane-enriched diet enhances lifespan of beetles from 15 to 30% (in certain conditions).
00:20:34 – Importance of low inflammation for longevity.
00:22:05 – Cruciferous vegetables and broccoli sprout powder seem to reduce a wide variety of inflammatory markers in humans.
00:36:32 – Sulforaphane improves learning in model of type II diabetes in mice.
00:37:19 – Sulforaphane and duchenne muscular dystrophy.
00:37:44 – Myostatin inhibition in muscle satellite cells (in vitro).
00:38:06 – Late-video recap: mortality and cancer, DNA damage, oxidative stress and inflammation, benzene excretion, cardiovascular disease, type II diabetes, effects on the brain (depression, autism, schizophrenia, neurodegeneration), NRF2 pathway.
00:40:27 – Thoughts on figuring out a dose of broccoli sprouts or sulforaphane.
00:41:01 – Anecdotes on sprouting at home.
00:43:14 – On cooking temperatures and sulforaphane activity.
00:43:45 – Gut bacteria conversion of sulforaphane from glucoraphanin.
00:44:24 – Supplements work better when combined with active myrosinase from vegetables.
00:44:56 – Cooking techniques and cruciferous vegetables.
00:46:06 – Isothiocyanates as goitrogens.
When the human body is confronted with harmful internal and external factors like toxins, the cells must rapidly trigger their antioxidant abilities to counteract oxidative stress. Because increased levels of oxidative stress have been determined to cause a variety of health issues, it’s important to use Nrf2 activation to take advantage of its benefits. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at�915-850-0900�.
Curated by Dr. Alex Jimenez
Additional Topic Discussion:�Acute Back Pain
Back pain�is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Because of this, injuries and/or aggravated conditions, such as�herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief. �
The number of Americans living to 100 — and beyond — has increased dramatically in recent decades, while those over the age of 80 comprise the world’s fastest-growing segment of the population, according to the latest research.
Between 1980 and 2014, life expectancy in the United States increased from 73.8 years to 79.1 years. Meanwhile, the number of Americans reaching and surpassing age 100 has exceeded 100,000, and that figure is expected to grow eight times — to 800,000 — by 2050, according to the National Institutes of Health and the U.S. Census Bureau.
So what’s the secret to living long enough to celebrate your 100th birthday?
While there are no sure-fire prescriptions for living to an extremely advanced old age, longevity researchers have found the ticket is a mixture of genetics and lifestyle — which means there are steps you can take to up your odds of living longer.
A landmark Swedish study, for example, showed that men who celebrated their 100th birthday all had mothers who lived into their 80s and 90s. But genetics wasn’t the only factor. The study also showed that the men had many controllable lifestyle factors in common. For instance:
All of them were non-smokers.
They generally stayed fit and trim by eating nutritious diets and exercising regularly.
Nearly all had healthy levels of cholesterol and blood pressure, which reduced their risk of developing cardiovascular disease, the No. 1 cause of death worldwide.
They owned their own homes or rented expensive residences, allowing them to live independently and stay mentally, physically, and socially active.
Most did not retire early, but instead actively worked until at least age 54.
None drank more than four cups of coffee per day.
Many reported having an optimistic outlook on life, which researchers said helped them embrace the power of positive thinking and combat stress and anxiety.
Studies of American centenarians have reached similar conclusions about the links between healthy lifestyles and longevity.
A recent study that compared and contrasted the lifestyles of Americans with the highest and lowest life expectancy found significant differences the daily habits of those individuals. For the study, researchers examined residents of Summit County, Colo., which has the nation’s highest life expectancy (86.8 years, two years higher than that of Andorra, the tiny country with the world’s highest life expectancy) and Lakota County, S.D. — which has the nation’s lowest life expectancy (66.8 years, comparable to Third World countries such as Sudan.
Researchers concluded that 74 percent of this disparity can be explained by controllable risk factors such as levels of physical activity, diet, tobacco use, and obesity, which increases the risk of developing life-threatening conditions diabetes, high blood pressure, heart disease, and certain cancers.
Worldwide, the rate of chronic illnesses such as heart disease is lowest in the Okinawa Archipelago, a group of 161 coral islands in the East China Sea that are home to the Earth’s longest-living people.
Here are some of the reasons why so many of them live to 100:
Diet. Okinawans primarily rely on plant sources such as sweet potatoes, greens, and whole grains. They supplement their diet with two or three servings per week of freshly caught fish, soya products, and an occasional serving of boiled pork with the fat trimmed off. They also drink antioxidant-rich green tea supplemented with jasmine flowers.
Exercise. Since most Okinawans are fishermen or farmers, they usually work outdoors into extreme old age. They get additional exercise from walking, gardening, martial arts and traditional dance.
Social life. Like other long-lived people, Okinawans maintain close social ties.
Stress. They also engage in stress-relieving strategies such as regular meditation.
Another longevity hot spot is the Greek island of Symi, where residents routinely live into their 90s. They, too, rely on fruits, vegetables, fish, and little meat. But they tend to slather their food tomato sauce, extra virgin olive oil and garlic. They also drink red wine with most meals, which helps account for their low rate of heart attacks.
So how long can life expectancy to continue to grow?
McGill University biologists Bryan G. Hughes and Siegfried Hekimi attempted to answer that question by analyzing the genetics and lifestyles of the longest-living individuals from the U.S., U.K., France, and Japan.
Their findings, published in the journal Nature, explodes the commonly held belief that the upper limit of the human lifespan is around 115 years.
“We just don’t know what the age limit might be. In fact, by extending trend lines, we can show that maximum and average lifespans, could continue to increase far into the foreseeable future,” Hekimi says.
It’s impossible to predict what future lifespans in humans might look like, Hekimi says. Some scientists argue that technology, medical interventions, and improvements in living conditions could all push up the upper limit.
A natural compound found in strawberries called fisetin reduces the mental effects of aging, says a study published in the Journals of Gerontology Series A. Researchers found it could help treat age-related mental decline and conditions like Alzheimer’s or stroke.
“Companies have put fisetin into various health products but there hasn’t been enough serious testing of the compound,” says Pamela Maher, a senior staff scientist in Salk’s Cellular Neurobiology Laboratory and senior author of the paper.
“Based on our ongoing work, we think fisetin might be helpful as a preventive for many age-associated neurodegenerative diseases, not just Alzheimer’s,” she said.
Maher has been studying fisetin, which is a type of flavonol that has powerful antioxidant properties, for more than a decade. Previous research found that it reduced memory loss related to Alzheimer’s disease (AD) in mice genetically modified to develop the disease.
When the scientists studied mice with Alzheimer’s, they found that the pathways involved in cellular inflammation were turned on. However, when the mice were given fisetin, they began producing anti-inflammatory molecules, and both memory loss and learning impairments were prevented. That particular research focused on genetic AD, which accounts for only 1 to 3 percent of cases.
For the recent study, Maher used a strain of laboratory mice that age prematurely and show signs of the disease at about 10 months in comparison to signs of physical and mental decline not seen in normal mice until two years of age.
The researchers fed the 3-month-old prematurely aging mice a daily dose of fisetin with their food for 7 months. Another group of the prematurely aging mice was fed the same food without fisetin.
During the study period, mice took various activity and memory tests. The team also examined levels of specific proteins related to brain function, as well as stress and inflammation.
“At 10 months, the differences between these two groups were striking,” says Maher, who hopes to conduct human trials. Mice not treated with fisetin had difficulties with all the cognitive tests as well as elevated markers of stress and inflammation. Brain cells called astrocytes and microglia, which are normally anti-inflammatory, were now driving rampant inflammation.
On the other hand, mice treated with fisetin were not noticeably different in behavior, cognitive ability or inflammatory markers at 10 months than a group of untreated 3-month-old mice with the same condition. In addition, fisetin was found to be safe even at high doses.
Strawberries have also been found to fight esophageal cancer. Chinese researchers gave volunteers freeze-dried strawberries each day for six months. A comparison of before-and-after biopsies showed that precancerous lesions in participants were decreased by 80 percent.
A handful of over-the-counter “personal sound amplification products” fared as well as an expensive hearing aid in helping people pick up more words in conversation, researchers report.
While the study took place in a sound booth, “in this controlled environment, some of these devices helped people with mild to moderate hearing loss as well as a hearing aid,” said study author Nicholas Reed. He is an audiologist at Johns Hopkins School of Medicine, in Baltimore.
An estimated 16 percent of Americans have trouble hearing, and the U.S. National Institute on Deafness and Other Communication Disorders estimates that almost 30 million people could benefit from hearing aids.
But hearing aids can cost thousands of dollars, and Medicare doesn’t cover them, the researchers noted.
“Hearing aids are regulated medical devices and should all be able to aid someone with hearing loss,” Reed said. “While not all hearing aids are the same, they should all be able to meet this minimum requirement of making sound louder at appropriate frequencies and with minimal distortion.”
In contrast, personal sound amplification products, available at stores and online, aren’t regulated and can’t be marketed as hearing aids. The U.S. Food and Drug Administration says they’re supposed to be used by people without hearing problems to help them hear distant sounds. The devices fit in or around the ear and make use of Bluetooth technology.
People do use the devices as hearing aids, however, said Todd Ricketts, vice chair of graduate studies with the department of hearing and speech sciences at Vanderbilt University Medical Center in Nashville. But these products tend to be less technologically advanced than hearing aids, although some offer advanced features.
Should you go out and buy one of the amplification devices instead of getting a hearing aid from a hearing specialist? Some audiologists will refuse to fit you for one, and the U.S. government doesn’t consider them appropriate for people with hearing loss.
For the study, researchers recruited 42 patients at a university audiology clinic who had mild to moderate hearing loss. Two-thirds were women, and their average age was 72.
In a sound booth, the participants listened to sentences with “speech babble noise” in the background. The participants tried to understand what was said without any hearing assistance; while using a hearing aid (costing $1,910); and while using personal sound amplification products bought online and at a pharmacy (one was $30, and the others cost between $270 and $350).
The researchers measured the average accuracy — the percentage of the time that the participants understood the sentences. It was 77 percent without a hearing aid, 88 percent with the hearing aid, and 81 to 87 percent with four of the amplification devices (Sound World Solutions CS50+, Soundhawk, Etymotic Bean and Tweak Focus).
“The results suggest that the devices are technologically and objectively capable of improving speech understanding in persons with hearing loss,” Reed said.
A fifth amplification device, the $30 MSA 30X Sound Amplifier, scored the worst, with an average accuracy level of 65 percent, the researchers reported. Reed said the device caused distortion.
Reed added that the findings suggest that both hearing aids and the amplification devices should be regulated and available over-the-counter. In that case, he said, “the FDA would set technical standards for all of these devices.”
For now, he said, adults with mild to moderate hearing loss may want to consider using one of the devices and consult an audiologist if needed to adjust it.
Ricketts cautioned that “the downside of just trying these or ordering them is that they may not be appropriate. People aren’t very good at self-diagnosing how much hearing loss they have.”
That’s where an audiologist could be helpful, he said, but some won’t sell these devices.
The study was published in the July 4 issue of the Journal of the American Medical Association.
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