For individuals looking to improve heart health, can consuming prunes help support cardiovascular health?
Prunes and Heart Health
Prunes, or dried plums, are fiber-rich fruits that are more nutrient-dense than fresh plums and help digestion and bowel movement. (Ellen Lever et al., 2019) New research suggests they could offer more than digestion and constipation relief, according to new studies presented at the American Society for Nutrition. Eating prunes daily can improve cholesterol levels and reduce oxidative stress and inflammation.
Eating five to 10 prunes a day may support heart health.
Heart health benefits of regular consumption were seen in men.
In older women, regularly eating prunes had no negative effect on total cholesterol, blood sugar, and insulin levels.
Another study found that eating 50–100 grams or five to ten prunes daily was associated with reduced heart disease risks. (Mee Young Hong et al., 2021)
The reductions in cholesterol and inflammation markers were because of improvements in antioxidant levels.
The conclusion was that prunes can support cardiovascular health.
Prunes and Fresh Plums
Although studies have suggested that prunes can support heart health, that doesn’t mean fresh plums or prune juice can offer the same benefits. However, there are not many studies on the benefits of fresh plums or prune juice, but it is possible that they would. However, further research is needed. Fresh plums that have been dried in hot air improve the nutritional value and shelf life of the fruit, which could be the reason the dried version retains more nutrients. (Harjeet Singh Brar et al., 2020)
Individuals may have to eat more plums to acquire the same benefits.
Eating 5–10 prunes seems to be easier than trying to equal the same amount, or more, of fresh plums.
But either option is recommended instead of prune juice as whole fruits have more fiber, make the body feel fuller, and are lower in calories.
Benefits For Young Individuals
Most of the research has been conducted on postmenopausal women and men over 55, but younger individuals can also benefit from eating prunes. A diet that is rich in fruits and vegetables is considered healthy, so adding prunes to one’s diet will add to health benefits. For individuals who don’t like prunes, fruits like apples and berries are also recommended for heart health. However, fruits only make up one part of the diet, and it is important to focus on a balanced diet with vegetables, legumes, and heart-healthy oils. Prunes contain a lot of fiber, so individuals are recommended to add them slowly into their daily routine, as adding too much at once can lead to cramping, bloating, and/or constipation.
Conquering Congestive Heart Failure
References
Lever, E., Scott, S. M., Louis, P., Emery, P. W., & Whelan, K. (2019). The effect of prunes on stool output, gut transit time and gastrointestinal microbiota: A randomised controlled trial. Clinical nutrition (Edinburgh, Scotland), 38(1), 165–173. doi.org/10.1016/j.clnu.2018.01.003
Hong, M. Y., Kern, M., Nakamichi-Lee, M., Abbaspour, N., Ahouraei Far, A., & Hooshmand, S. (2021). Dried Plum Consumption Improves Total Cholesterol and Antioxidant Capacity and Reduces Inflammation in Healthy Postmenopausal Women. Journal of medicinal food, 24(11), 1161–1168. doi.org/10.1089/jmf.2020.0142
Harjeet Singh Brar, Prabhjot Kaur, Jayasankar Subramanian, Gopu R. Nair & Ashutosh Singh (2020) Effect of Chemical Pretreatment on Drying Kinetics and Physio-chemical Characteristics of Yellow European Plums, International Journal of Fruit Science, 20:sup2, S252-S279, DOI: 10.1080/15538362.2020.1717403
Dr. Alex Jimenez, D.C., presents how chronic stress can impact the body and how it is correlated with inflammation in this 2-part series. Part 1 examined how stress correlates with various symptoms affecting the body’s gene levels. Part 2 looks at how inflammation and chronic stress correlate with the various factors that can lead to physical development. We refer our patients to certified medical providers who provide available treatments for many individuals suffering from chronic stress associated with the cardiovascular, endocrine, and immune systems affecting the body and developing inflammation. We encourage each of our patients by mentioning them to associated medical providers based on their analysis appropriately. We understand that education is a delightful way when asking our providers questions at the patient’s request and understanding. Dr. Jimenez, D.C., only uses this information as an educational service. Disclaimer
How Stress Can Impact Us?
Dr. Alex Jimenez, D.C., presents: Stress can create many emotions that can hugely impact many of us. Whether it is anger, frustration, or sadness, stress can make anyone reach a breaking point and cause underlying conditions that can develop into cardiovascular issues. So those people with the highest level of anger, when you look at the cardiovascular literature, have the least probability of survival. Anger is a bad player. Anger causes arrhythmia. This study looked at, now that we have people with ICDs and defibrillators, we can monitor these things. And we see that anger can trigger ventricular arrhythmias in patients. And it’s easy now to follow, with some of our technology.
Anger has been linked to episodes of atrial fibrillation. When you think about it, it’s adrenaline outpouring into the body and causing coronary constriction. It’s increasing the heart rate. All of these things can lead to arrhythmia. And it doesn’t have to be AFib. It can be APCs and VPCs. Now, some very interesting research has come out about telomerase and telomeres. Telomeres are little caps on the chromosomes, and telomerase is the enzyme linked to telomere formation. And now, we can understand through the language of science, and we’re starting to use technology and use science in a way that we could never do before to understand the impact of stress on telomeres and telomerase enzymes.
The Factors That Lead Up To Chronic Stress
Dr. Alex Jimenez, D.C., presents: So one of the key people to study this is the Nobel Prize-winning, Dr. Elizabeth Blackburn. And what she said is that this is a conclusion, and we’ll come back to some of her other studies. She tells us that the telomeres of babies from women in utero had a lot of stress or were even shorter in young adulthood compared to mothers who did not have the same stressful situations. Maternal psychological stress during pregnancy may exert a programming effect on the developing telomere biology system that is already apparent at birth as reflected by the setting of newborn leukocyte telemetry length. So children can come in imprinted, and even if they do, this can be transformed.
What about racial discrimination these boxes here show high racial discrimination leading to low telomere length, which most of us have ever thought about. So, shorter telomere length leads to an increased risk of cancer and overall mortality. Cancer incidence rates are 22.5 per 1000 person-years in the shortest telomere group, verse 14.2 in the middle group, and 5.1 in the longest telomere group. Shorter telomeres can lead to instability of the chromosome and result in cancer formation. So, now we understand, through the language of science, the impact of stress on the telomerase enzyme and the telomere length. According to Dr. Elizabeth Blackburn, 58 premenopausal women were caregivers of their chronically ill children verse women who had healthy children. The women were asked how they perceive stress in their lives and whether it impacts their health by affecting their cellular aging.
That was the question of the study as they looked at telomere length and telomerase enzyme, and this is what they found. Now, the keyword here is perceived. We are not to judge each other’s stress. Stress is personal, and some of our responses may be genetic. For example, someone who has homozygous comps with a sluggish gene may have much more anxiety than someone who doesn’t have this genetic polymorphism. Someone who has an MAOA in an MAOB may have more anxiety than someone who doesn’t have that genetic polymorphism. So there is a genetic component to our response, but what she found was perceived psychological stress. And the number of years caring for chronically ill children was associated with shorter telomere length and less telomerase activity, providing the first indication that stress can impact telomere maintenance and longevity.
How To Transform Our Stress Response?
Dr. Alex Jimenez, D.C., presents: That’s powerful, and many healthcare providers are under some form of stress. And the question is, what can we do to transform our response? Framingham also looked at depression and identified clinical depression as a bigger risk for cardiovascular events and poor outcomes than smoking, diabetes, high LDL, and low HDL, which is crazy because we spend all of our time on these things. Yet, we don’t spend much time dealing with the emotional aspects of vascular disease. This is affected depression, inventory, a simple screening test for depression, looking at people with high levels of depression versus low levels of depression. And you can see that as you go from the low to the highest level, as you work your way through, the chance of survival becomes less.
And many of us have our theories as to why this occurs. And is it because if we are depressed, we don’t say, “Oh, I’m going to eat some brussels sprouts, and I’m going to take those B vitamins, and I’m going to go out and exercise, and I’m going to do some meditation.” So post-MI independent risk factor for an event is depression. Our mindset regarding depression makes us incapable of functioning normally and can make our bodies develop issues that affect our vital organs, muscles, and joints. So, depression is a big player, as 75% of post-MI deaths are related to depression, right? So looking at patients, now, you have to ask the question: Is it the depression causing the problem, or is it the cytokine sickness that’s already led to the heart disease causing the depression? We have to factor all of this in.
And yet another study looked at over 4,000 people with no coronary disease at baseline. For every increase of five points on the depression scale, that increased risk by 15%. And those with the highest depression scores had a 40% higher coronary artery disease rate and a 60% higher death rate. So mostly everyone thinks it’s a cytokine sickness that leads to MI, vascular disease, and depression. And then, of course, when you have an event, and you come out with a whole host of issues around it, we know that people who are depressed have a twofold increase in mortality, a fivefold increase in death after a heart attack, and poor outcomes with surgery. It’s like this, what came first, the chicken or the egg?
How Depression Is Linked With Chronic Stress?
Dr. Alex Jimenez, D.C., presents: Every surgeon knows this. They don’t want to do surgery on depressed people. They know the outcome is not good, and of course, they are less likely to follow through on all of our great functional medicine recommendations. So what are some of the mechanisms of autonomic dysfunction have been evaluated heart rate variability and low levels of omega-3s, which have a profound effect on the brain, and low levels of vitamin D. There are those inflammatory cytokines we talked about not getting restorative sleep, and many of our heart patients do have apnea. And remember, don’t just think it’s the heavyset heart patients with thick short necks; it can be quite deceiving. And it’s really important to look at the structure of the face and, of course, social connection, which is the secret sauce. So is autonomic dysfunction a mechanism? One study looked at heart rate variability in people with a recent MI, and they looked at over 300 people with depression and those without depression. They found that four heart rate variability indices will lower in people with depression.
Gut Inflammation & Chronic Stress
Dr. Alex Jimenez, D.C., presents: So here are two groups of people having a heart attack and heart rate variability, rising to the top as a possible etiology. One of the many things that can also affect chronic stress in the body is how the gut microbiome plays its part in oxidative stress. The gut is everything, and many heart patients laugh because they would ask their cardiologists, “Why do you care about my gut microbiome? Why would this affect my heart?” Well, all that gut inflammation is causing cytokine sickness. And what a lot of us have forgotten since medical school is that many of our neurotransmitters come from the gut. So chronic inflammation and exposure to inflammatory cytokines appear to lead to alterations in dopamine function and the basal ganglia, reflected by depression, fatigue, and psychomotor slowing. So we can’t emphasize the role of inflammation and depression enough if we take a look at acute coronary syndrome and depression, which was associated with higher markers for inflammation, more elevated CRP, lower HS, lower heart rate variability, and something that never gets checked in the hospital, which is nutrition deficiencies.
And in this case, they looked at omega-3s and vitamin D levels, so at a minimum, an omega-3 check and a vitamin D level are warranted in all of our patients. And certainly, if you can get a full diagnosis for stress-induced inflammation. Another condition you must look at when it comes to stress-induced inflammation is osteoporosis in the joints. Many people with osteoporosis will have muscle loss, immune dysfunction, fat around the midline, and high blood sugar are associated with aging, and it can come from elevated cortisol levels in the body.
High cortisol heart disease risks are two times higher in people taking high doses of steroids. Small amounts of steroids don’t have the same risk, so it is not as big a deal. Of course, we try to get our patients off of steroids. But the point here is that cortisol is a stress hormone and is a stress hormone that raises blood pressure and puts weight on the midline, makes us diabetic, causes insulin resistance, and the list is endless. So, cortisol’s a big player, and when it comes to functional medicine, we have to look at the various tests that pertain to elevated levels of cortisol like food sensitivity, a 3-day stool valve, a nutra-valve, and an adrenal stress index test to look at what is going on with the patients. When there is a heightened sympathetic nervous system and high cortisol, we discussed everything from coagulopathy to decreased heart rate variability, central obesity, diabetes, and hypertension.
Parental Relationships & Chronic Stress
Dr. Alex Jimenez, D.C., presents: And turning on the renin-angiotensin system it’s all linked to stress. Let’s look at this study that looked at 126 Harvard Medical students, and they were followed for 35 years, a long research. And they said, what’s the incidence of significant illness, heart disease, cancer, hypertension? And they asked these students very simple questions, what was your relationship with your mom and your dad? Was it very close? Was it warm and friendly? Was it tolerant? Was it strained and cold? This is what they found. They found that if the students identified their relationship with their parents as strained 100% incidence of significant health risk. Thirty-five years later, if they said it was warm and close, the results cut that percentage in half. And it would help if you thought about what it is and what can explain this, and you’ll see how adverse childhood experiences make us sick in a few minutes and how we learn our coping skills from our parents.
Conclusion
Dr. Alex Jimenez, D.C., presents: Our spiritual tradition comes from our parents often. Our parents are the ones who frequently teach us how to get angry or how to resolve conflict. So our parents have had a profound effect on us. And when you think about that, our connection is also not very surprising. This is a 35-year follow-up study.
Chronic stress can lead to multiple issues that can correlate to illness and dysfunction in the muscles and joints. It can affect the gut system and lead to inflammation if it is not taken care of immediately. So when it comes to the impact of stress affecting our daily lives, it can be numerous factors, from chronic conditions to family history. Eating nutritious foods high in antioxidants, exercising, practicing mindfulness, and going to daily treatments can lower the effects of chronic stress and reduce the associated symptoms that overlap and cause pain to the body. We can continue with our health and wellness journey pain-free by utilizing various ways to lower chronic stress in our bodies.
Dr. Alex Jimenez, D.C., presents how stress can impact many individuals and correlate with many conditions in the body in this 2-part series. We refer our patients to certified medical providers who provide multiple available treatments for many people suffering from hypertension associated with the cardiovascular, endocrine, and immune systems affecting the body. We encourage each of our patients by mentioning them to associated medical providers based on their analysis appropriately. We understand that education is a delightful way when asking our providers questions at the patient’s request and understanding. Dr. Jimenez, D.C., only uses this information as an educational service. Disclaimer
How Stress Impacts the Body
Dr. Alex Jimenez, D.C., presents: Now everyone responds to changes in the environment differently. When it comes to many individuals doing everyday activities from working at their job, opening on the weekends, traffic jams, taking exams, or preparing for a big speech, the body goes through a constant state of hyperreactive to a stage of emotional, mental exhaustion that leaves the individual to be exhausted and stressed out. And the key is to recognize this before it happens, as we see this impact of stress on our patients and ourselves. And the first thing to realize is what the initiating event is causing this impact.
Whatever the initiating event, the most important part is our perception of the event. What does it mean to us? Is it our perception? When the body goes through this initiating event, it can cause the perception to lead to the response and the effect on our body. So perception is everything as we talk about stress and the stress response. Now, we have over 1400 chemical reactions that occur in the body. So for this talk’s purpose, we’ll discuss the three key ones: adrenaline and neuro-adrenaline, aldosterone, and of course, cortisol.
And why are these important? Because every one of these has a huge impact on cardiovascular disease. Now, in the 1990s, many doctors were starting to understand the effect of stress on the physical body. And what happens to people when their HPA-axis signals that they are under threat and start flooding their bodies with stress hormones? Well, we see enhanced coagulation. We see a shift in the renin and angiotensin system. It revs up. We see weight gain in people and insulin resistance. What a lot of people don’t realize is that lipids become abnormal with stress. Almost every one of our patients knows that tachycardia and arrhythmia occur when our adrenaline is flowing, and our blood pressure increases. Now, think about this through the language of medicine.
Around the 1990s, doctors were giving aspirin and Plavix at the time for coagulation. We continue to provide ACEs and ARBs to our patients. The impact of cortisol causes weight gain and insulin resistance. We give statins; we give metformin. We provide beta blockers for that, tachycardia, and calcium blockers for that high blood pressure. So every single hormone that gets turned on with stress, we have a drug that we’re using to balance that. And quite frankly, for years, we talked about how good beta blockers were for the heart. Well, when you think about that, beta blockers do block adrenaline. So when doctors look at this, they begin to think, “Well, maybe we need to medicate and meditate, right? We’re using all these drugs, but we may need to look at other ways to transform the stress response.”
What is Vasoconstriction?
Dr. Alex Jimenez, D.C., presents: We won’t read every one of these symptoms because there are so many, but it all comes down to the same thing. Stress. We have to think of someone who’s in an auto accident, for example, and that person is bleeding. So the body is beautiful in that it puts together a way to stop the individual from bleeding or vasoconstriction. Vasoconstriction is constructing these blood vessels and making the platelets sticky so they form a clot, and the blood can stop. This increases the cardiac output by raising the heart rate and increases aldosterone, which causes salt and water retention to raise the blood pressure. So for someone in a medical emergency, like an accident, bleeding, or losing volume, this is the beauty of the human body. But unfortunately, we see people living this way, literally 24/7. So we know the vasoconstriction and the platelet stickiness, and we see increases in markers for inflammation, homocysteine, CRP, and fibrinogen, all of which increase cardiovascular risk.
We see the impact of cortisol, not only raising blood pressure, not only causing diabetes and insulin resistance, but also depositing abdominal fat around the midline. And then, as you’ll see in a few minutes, there are links between stressful events and arrhythmias like atrial fibrillation and even ventricular fibrillation. For the first time in medicine, in cardiology, we have a syndrome called takosubo cardiomyopathy, which is affectionately called broken heart syndrome. And this is a syndrome in which the myocardium becomes acutely stunned to the point of causing severe left ventricular function or dysfunction. And usually, this is triggered by bad news and an emotionally stressful event. It looks like someone needs a heart transplant. So when we think about the old Framingham risk factors, we say, which of these are impacted by stress?
Symptoms of Stress
Dr. Alex Jimenez, D.C., presents: People have all sorts of maladaptive behaviors to stress, whether 20 friends in this pack of cigarettes, eating this Cinnabon because it makes me feel good right now, or all the cortisol will make me fat and diabetic. Lipids go up under stress; blood pressure goes up under stress. So every one of these risk factors is impacted by stress hormones. And, of course, we know that with the turning on of the RAS system or the renin-angiotensin system, we always see a worsening in heart failure. And this is very much described in the literature. And, for those of you who may work in the emergency room, ask your patients what they were doing before coming in with their episode of congestive heart failure or chest pain. And you’re going to hear stories like, I was watching a bad movie, or I was watching a war movie, or I got upset over the football game, or something like that.
We’ll talk about heart rate variability, which gets impacted by stress. And, of course, stress affects our ability to resist infections. And we know that people are under stress when they’re vaccinated. For example, Cleco lasers work but don’t produce antibodies to the vaccine when they’re under stress. And, of course, as you’ll see in a minute, severe stress can cause sudden cardiac death, MI, and so on. So it is a bad player that’s overlooked. And for many of our patients, stress drives the train. So when we’re talking about eating brussels sprouts and cauliflower and, you know, lots of green leafy vegetables, and someone is under so much stress that they’re trying to figure out, “How am I going to get through the day?” They’re not hearing any of the other things that we’re recommending.
So, chronic stress and affective disorders, whether depression, anxiety, or panic, put our foot on the accelerator and rev up the sympathetic nervous system. We know that the same things we see with aging, as you’ll see in a minute, are linked to increased levels of stress hormones, especially cortisol. So whether it’s osteoporosis, decreased bone density, endothelial dysfunction, platelet activation, hypertension, central obesity, or insulin resistance, this comes from a stress response. And we have to have a plan for our patients on how to handle this. American Institute of Stress says that 75 to 90% of all healthcare provider visits result from stress-related disorders. And that’s way too high, but by looking at the patients and where they were coming in with, they tell their stories to their doctors. The results are the same; it doesn’t matter whether it was headaches, muscle tension, angina, arrhythmia, or irritable bowel; it almost always had some stress trigger.
Acute & Chronic Stress
Dr. Alex Jimenez, D.C., presents: There’s a difference between acute and chronic stress with our perception and social connection. Even though we gain some strength from a higher power, stress can impact anyone, and most of us might not be able to handle it well. So a great study was done many years ago by Dr. Ray and Holmes that stated, 50 years ago, put together a method for quantifying life-changing events. So let’s look at some areas, such as life-changing events. How do life-changing events and how do they rank? Which are the big ones, and which are the little ones?
And how does that ranking lead to major medical problems like cancer, heart attack, and sudden death in the future? So they looked at 43 life-changing events, ranked them originally, and re-ranked them in the 1990s. And some of them remained the same. They gave an adjustment score to the event, and then they looked at numbers that would be linked to major illness. So, for example, a life-changing event. Number one, 100 life-changing units, is a death of a spouse. Anyone could relate to that. Divorce was number two, separation number three, and the end of a close family member. But also noticed that some things got ranked that are, you might not equate with, being a major life-changing event that can impact a stress response like marriage or retirement.
Conclusion
Dr. Alex Jimenez, D.C., presents: So it wasn’t the actual single event that made the difference. It was the adding up of events. And what they found after looking at 67 physicians was if you had a life-changing unit score of somewhere between zero and one 50, not a big deal, no real major illness, but once you hit that 300 mark, there was a 50% chance of major illness. So this timeline of events in the patient’s life. We want to know what was going on in their life when their symptoms started and then bring it back earlier to understand the environment in which this individual was living. The impact of stress can make many individuals develop chronic conditions and mask other symptoms that can lead to muscle and joint pain. In part 2, we will dive in more about how the impact of stress affects a person’s body and health.
Kombucha is a fermented tea that has been around for nearly 2,000 years. It became popular in Europe in the early 20th century. It has the same health benefits as tea, is rich in probiotics, contains antioxidants, and can destroy harmful bacteria. Kombucha sales are growing at stores because of its health and energy benefits.
Kombucha
It is typically made with black or green tea, sugar, healthy bacteria, and yeast. It is flavored by adding spices or fruits into the tea while it ferments. It is fermented for about a week, when gases, 0.5 percent of alcohol, beneficial bacteria, and acetic acid are produced. The fermentation process makes the tea slightly effervescent. It contains B vitamins, antioxidants, and probiotics, but the nutritional content will vary depending on the brand and its preparation.
Benefits
The benefits include:
Improved digestion from the fact that fermentation makes probiotics.
Helps with diarrhea and irritable bowel syndrome/IBS.
Toxin removal
Increased energy
Improved immune system health
Weight loss
Helps with high blood pressure
Heart disease
Kombucha, made from green tea, includes the benefits of:
Beneficial bacteria are known as probiotics. These same probiotics are found in other fermented foods, like yogurt and sauerkraut. Probiotics help populate the gut with healthy bacteria that aid digestion, reduce inflammation, and produce essential vitamins B and K. The probiotics improve bowel movements and alleviate nausea, bloating, and indigestion.
Antioxidants
The antioxidants and polyphenols benefits include:
Increased metabolic rate
Reduced blood pressure
Lowered cholesterol
Improved cognitive function
Decreased risk of chronic diseases – cardiovascular disease, type 2 diabetes, and certain cancers.
Anti-Bacterial Properties
The fermentation process produces acetic acid that destroys harmful pathogens like invasive bacteria and yeasts, preventing infection.
The anti-bacterial effect also preserves the beneficial bacteria.
Liver Detoxification
It can help detoxify the liver, which:
Improves overall skin health
Improves liver function
Decreases abdominal bloating and pain
Improves digestion and bladder function
Pancreatic Support
It can improve pancreatic function, which can help protect the body from diseases and illnesses like:
Acid reflux
Abdominal spasms
Numbness
Pancreatic cancer
Joint Support
The tea contains compounds like glucosamines that have been shown to improve joint health and relieve joint pain.
Glucosamines increase hyaluronic acid, lubricating the joints, which helps protect and strengthen them.
Satisfy Soda Craving
The variety of flavors and natural carbonation can satisfy the craving for a soda or other unhealthy beverages.
Injury Medical Chiropractic and Functional Medicine Clinic includes elements of integrative medicine and takes a different approach to health and wellness. Specialists take a comprehensive view of an individual’s health, recognizing the need for a personalized treatment plan to help identify what is needed to get healthy. The team will create a customized plan that fits an individual’s schedule and needs.
Dietitian Explains Kombucha
References
Cortesia, Claudia et al. “Acetic Acid, the active component of vinegar, is an effective tuberculocidal disinfectant.” mBio vol. 5,2 e00013-14. 25 Feb. 2014, doi:10.1128/mBio.00013-14
Costa, Mirian Aparecida de Campos et al. “Effect of kombucha intake on the gut microbiota and obesity-related comorbidities: A systematic review.” Critical reviews in food science and nutrition, 1-16. 26 Oct. 2021, doi:10.1080/10408398.2021.1995321
Gaggìa, Francesca, et al. “Kombucha Beverage from Green, Black and Rooibos Teas: A Comparative Study Looking at Microbiology, Chemistry and Antioxidant Activity.” Nutrients vol. 11,1 1. 20 Dec. 2018, doi:10.3390/nu11010001
Kapp, Julie M, and Walton Sumner. “Kombucha: a systematic review of the empirical evidence of human health benefit.” Annals of epidemiology vol. 30 (2019): 66-70. doi:10.1016/j.annepidem.2018.11.001
Villarreal-Soto, Silvia Alejandra, et al. “Understanding Kombucha Tea Fermentation: A Review.” Journal of food science vol. 83,3 (2018): 580-588. doi:10.1111/1750-3841.14068
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.
IFM's Find A Practitioner tool is the largest referral network in Functional Medicine, created to help patients locate Functional Medicine practitioners anywhere in the world. IFM Certified Practitioners are listed first in the search results, given their extensive education in Functional Medicine
