People who have Heart Problems report that their symptoms have decreased after taking an Nrf2 activator. Following the testimonials are current research articles that report new information about the cause of Heart Problems and how Nrf2 activators can be effective in treating them at the cellular level where they start.
Frank Paquin: "A couple of years ago they brought me in. I had numerous heart attacks. They wound up putting in 5 stents and 4 balloons because my arteries were getting clogged up. I couldn't breathe. I couldn't take a bath without having to do it in two stages. I didn't have the strength or the breath it took to take a shower all at one time. Things progressively got worse. In December I was diagnosed with diastolic heart failure. They told me I was getting fibrosis of the heart. My heart would compress but it didn't have the strength to pump the blood back out to my lungs and my brain. I was having migraines and chest pains so bad that I was taking two and three nitroglycerine pills at a time because of the chest pain. The doctor said they couldn't do anything. My blood pressure was 95 to 100 plus over 150 to 160. It was really bad....
"Then someone brought me a DVD showing the effects of Protandim. I had never heard of it, and I really didn't want to take another pill, but after a couple of weeks of that DVD sitting in my kitchen I decided to watch the video. Once I watched it I researched more on the computer and I decided that night I was going to take it. The next day I called a distributor, ordered a bottle, and he gave me some to take while my order came in. I started taking Protandim the beginning of April, and within two weeks the abdominal pain ceased. I had no more abdominal pain. The diarrhea was cut more than half. I started backing off the steroids and codeine pills. Within three weeks I was completely off the steroids and codeine, and I had no abdominal pain, no diarrhea and no chest pains.
"The Protandim, what it did for my body, got rid of all the poisonous radicals I had in my body. I was taking some 39 pills every day, and now I take one Protandim, a fish oil pill and one blood pressure medication where I was taking three before. And I have no problem. youtube.com, search "Protandim"
(No name given): Before I started taking PROTANDIM, I had high cholesterol, neuropathy of my feet and severe neck pains. I started taking PROTANDIM in May of this year and all I can tell you is things started to CHANGE.
First I had a doctor appointment in July just 30 days after taking PROTANDIM and as always they drew my blood to check my cholesterol levels, because my cholesterol levels had been around 235 to 240 over the past 3 years. Now let me tell you I was doing everything to lower it. I changed my eating habits and I started taking Lipitor, but that didn’t work. Then I changed to Crestor and still that didn’t work All I got was pains in my kidneys and pains in liver, so I changed to Red Yeast Rice because I was told how great it worked. Well I went back to my doctor and still NO CHANGE with my cholesterol. I was frustrated and then a friend introduced me to PROTANDIM back in October.
At first I was hesitant and didn’t believe a supplement could help me, so I read up on it. I ran into him again 2 months later and he asked me if I started taking PROTANDIM and I said no…He replied, “Trust Me it works.” I said ok and like most of us I blew it off.
Well let me tell you it was the DUMBEST thing I ever did because I ran into him in May and I finally said YES. – And guess what? It WAS THE SMARTEST THING I EVER DID. I buy PROTANDIM and began taking my supplement DAILY.
At first I was thinking I was going to feel something. I was being like all of us, I was being skeptical, but guess what I STARTED TO notice little things after 7 days. I was no longer having problems going to the bathroom…I was regular again. Then I noticed the aches and pains weren’t there anymore. But it didn’t stop there, my neuropathy that was flaring up and my feet were NO LONGER cramping. I was HAPPILY AMAZED.
Now here is what proved it works and keeps working for my body. I went to the doctor 30 days after taking PROTANDIM. I waited for my results and when I called in the nurse told me that my cholesterol was 160…can you believe it? 160!
The nurse was shocked and asked me what I am doing that helped me reach the number I was at in my 20’s and 30’s. I was EXTACTIC!
I’m feeling great and my body is FUNTIONING on ALL BARRELLS like a car. NO MORE ACHES, NO MORE PAIN, NO MORE NEUROPATHY and LOWER CHOLESTEROL. All thanks to PROTANDIM. (from livelifehealer.wordpress.com).
"Within two months of being on it, at the oncologist's, the doctor said I looked so good that he was not going to go on with the chemo medicines that he was giving me, and that he would see me in six months. The next physician I saw was my eye doctor. She said, you don't need to change your glasses this time. Your eyes are holding so well. So it was the first time in a long time that I didn't have to have a new prescription. youtube.com, search "Protandim"
American ginseng is capable of ameliorating cardiac dysfunction and activating Nrf2, a master regulator of antioxidant defense, in the heart. This study was designed to isolate compounds from American ginseng and to determine those responsible for the Nrf2-mediated resolution of inflamed macrophage-induced cardiomyocyte hypertrophy.
MATERIALS AND METHODS:A standardized crude extract of American ginseng was supplied by the National Research Council of Canada, Institute for National Measurement Standards. A bioassay-based fractionization of American ginseng was performed to identify the putative substances which could activate Nrf2-mediated suppression of pro-inflammatory cytokine expression in macrophages and macrophage-mediated pro-hypertrophic growth in cardiomyocytes.
RESULTS:A hexane fraction of an anti-inflammatory crude extract of American ginseng was found to be most effective in suppressing the inflammatory responses in macrophages. Preparative, reverse-phase HPLC and a comparative analysis by analytical scale LC-UV/MS revealed the hexane fraction contains predominantly C17 polyacetylenes and linolenic acid. Panaxynol, one of the major polyacetylenes, was found to be a potent Nrf2 activator. Panaxynol posttranscriptionally activated Nrf2 by inhibiting Kelch-like ECH-associated protein (Keap) 1-mediated degradation without affecting the binding of Keap1 and Nrf2. Moreover, panaxynol suppressed a selected set of cytokine expression via the activation of Nrf2 while minimally regulating nuclear factor-kappa B (NF-κB)-mediated cytokine expression in macrophages. It also dramatically inhibited the inflamed macrophage-mediated cardiomyocyte death and hypertrophy by activating Nrf2 in macrophages.
CONCLUSIONS:These results demonstrate that American ginseng-derived panaxynol is a specific Nrf2 activator and panaxynol-activated Nrf2 signaling is at least partly responsible for American ginseng-induced health benefit in the heart.
Sulforaphane, a natural isothiocyanate compound found in cruciferous vegetables, has been shown to exert cardioprotective effects during ischemicheart injury. However, the effects of sulforaphane on cardiotoxicity induced by doxorubicin are unknown. Thus, in the present study, H9c2 rat myoblasts were pre-treated with sulforaphane and its effects on cardiotoxicity were then examined. The results revealed that the pre-treatment of H9c2 rat myoblasts with sulforaphane decreased the apoptotic cell number (as shown by trypan blue exclusion assay) and the expression of pro-apoptotic proteins (Bax, caspase-3 and cytochrome c; as shown by western blot analysis and immunostaining), as well as the doxorubicin-induced increase in mitochondrial membrane potential (measured by JC-1 assay). Furthermore, sulforaphane increased the mRNA and protein expression of heme oxygenase-1 (HO-1, measured by RT-qPCR), which consequently reduced the levels of reactive oxygen species (ROS, measured using MitoSOX Red reagent) in the mitochondria which were induced by doxorubicin. The cardioprotective effects of sulforaphane were found to be mediated by the activation of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor-2 (Nrf2)/antioxidant-responsive element (ARE) pathway, which in turn mediates the induction of HO-1. Taken together, the findings of this study demonstrate that sulforaphane prevents doxorubicin-induced oxidative stress and cell death in H9c2 cells through the induction of HO-1 expression.
We have recently shown that DJ-1 is implicated in the delayed cardioprotective effect of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R) injury as an endogenous protective protein. This study aims to further investigate the underlying mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress. Using a well-characterized cellular model of HPC from rat heart-derived H9c2 cells, we found that HPC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein-1 (Keap1) dissociation and resulted in increased nuclear translocation, antioxidant response elements (ARE)-binding and transcriptional activity of Nrf2 at 24 h after HPC, with subsequent upregulation of manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1), which provided the delayed protection against H/R-induced oxidative stress in normal H9c2 cells. However, the aforementioned effects of HPC were abolished in DJ-1-knockdown H9c2 cells, which were restored by restoration of DJ-1 expression. Importantly, we showed that inhibition of the Nrf2 pathway in H9c2 cells mimicked the effects of DJ-1 knockdown and abolished HPC-derived the induction of antioxidative enzymes (MnSOD and HO-1) and the delayed cardioprotection. In addition, inhibition of Nrf2 also reversed the effects of restored DJ-1 expression on induction of antioxidative enzymes and delayed cardioprotection by HPC in DJ-1-knockdown H9c2 cells. Taken together, the present work revealed that activation of Nrf2 pathway and subsequent upregulation of antioxidative enzymes could be a critical mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress in H9c2 cells.
JOURNAL ARTICLE (from pubmed.gov):
Stem Cells.<http://www.ncbi.nlm.nih.gov/pubmed/25826782> 2015 Mar 31. doi: 10.1002/stem.2015. [Epub ahead of print]
Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure.
Abstract
Danon disease is a familial cardiomyopathy associated with impaired autophagy due to mutations in the gene encoding lysosomal-associated membrane protein type 2 (LAMP-2). Emerging evidence has highlighted the importance of autophagy in regulating cardiomyocyte bioenergetics, function, and survival. However, the mechanisms responsible for cellular dysfunction and death in cardiomyocytes with impaired autophagic flux remain unclear. To investigate the molecular mechanisms responsible for Danon disease, we created induced pluripotent stem cells (iPSC) from two patients with different LAMP-2 mutations. Danon iPSC-derived cardiomyocytes (iPSC-CMs) exhibited impaired autophagic flux and key features of heart failure such as increased cell size, increased expression of natriuretic peptides, and abnormal calcium handling compared to control iPSC-CMs. Additionally, Danon iPSC-CMs demonstrated excessive amounts of mitochondrial oxidative stress and apoptosis. Using the sulfhydryl antioxidant N-acetylcysteine to scavenge free radicals resulted in a significant reduction in apoptotic cell death in Danon iPSC-CMs. In summary, we have modeled Danon disease using human iPSC-CMs from patients with mutations in LAMP-2, allowing us to gain mechanistic insight into the pathogenesis of this disease. We demonstrate that LAMP-2 deficiency leads to an impairment in autophagic flux, which results in excessive oxidative stress, and subsequent cardiomyocyte apoptosis. Scavenging excessive free radicals with antioxidants may be beneficial for patients with Danon disease. In vivo studies will be necessary to validate this new treatment strategy.
KEYWORDS:
PMID: 25826782 [PubMed - as supplied by publisher]
[INTERPRETATION: Danon disease causes heart cells to stop working, resulting in heart failure. This is because there are excessive amounts of oxidative stress (cell damage by free radicals) and apoptosis (cell death). Using an antioxidant, the free radicals are mopped up, resulting in a significant reduction of cell death and causing the cells to live and continue working. It looks like the use of antioxidants is the new treatment strategy for this heart problem.]
JOURNAL ARTICLE (from pubmed.gov):
J
Geriatr Cardiol. 2015 Jan;12(1):1-10. doi:
10.11909/j.issn.1671-5411.2015.01.001.
Abstract
OBJECTIVE:
To
investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine
activation in the transition of hypertensive heart disease to heart failure
with preserved ejection fraction (HFPEF).
We
performed echocardiography for 112 patients (≥ 60 years old) with normal EF (18
controls and 94 with hypertension), and determined protein carbonylation (PC),
and tetrahydrobiopterin (BH4), C-reactive protein (CRP), interleukin-6 (IL-6),
tumor necrosis factor-α (TNF-α), fibrinogen, plasminogen activator inhibitor
type-I (PAI-I), von Willebrand factor, chromogranin A (cGA) and B-type
natriuretic peptide (BNP) levels from their blood samples.
We
found that 40% (38/94) of the patients with hypertension (HT) had no diastolic
dysfunction (HTDD-), and 60% (56/94) had diastolic dysfunction (HTDD+).
Compared to the controls, both patient groups had increased PC and BH4, TNF-α,
PAI-I and BNP levels, while the HTDD+ group had elevated cGA and CRP levels. Decreased
atrial and longitudinal left ventricular (LV) systolic and diastolic myocardial
deformation (strain and strain rate) was demonstrated in both patient groups
versus the control. Patients whose LV diastolic function deteriorated during
the follow-up had elevated PC and IL-6 level compared to their own baseline
values, and to the respective values of patients whose LV diastolic function
remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels
inversely correlated with LV systolic, diastolic and atrial function.
In
patients with HT and normal EF, the most common HFPEF precursor condition, oxidative
stress and inflammation may be responsible for LV systolic, diastolic and
atrial dysfunction, which are important determinants of the transition of
HT to HFPEF.
PMID: 25678898
[PubMed] PMCID: PMC4308452
Free PMC Article
[INTERPRETATION: Oxidative stress (cell damage by oxidants) and inflammation may be responsible for heart problems, including hypertension and heart failure.]
JOURNAL ARTICLE (from
pubmed.gov)
Basic Res
Cardiol. 2015 Mar;110(2):470. Epub 2015 Feb 14.
Abstract
Heart
rupture and heart failure are deleterious complications of myocardial
infarction. The ShcA gene encodes for three protein isoforms, p46-, p52- and
p66ShcA. p66ShcA induces oxidative stress. We studied the role of
p66ShcA post-infarction. Expression of p66ShcA was analyzed in myocardium
of patients with stable angina (n = 11), in explanted hearts with
end-stage ischemic heart failure (n = 9) and compared to non-failing
hearts not suitable for donation (n = 7). p66ShcA was increased in
the patients with stable angina, but not in the patients with end-stage heart
failure. Mice (n = 105) were subjected to coronary artery ligation.
p66ShcA expression and phosphorylation were evaluated over a 6-week period.
p66ShcA expression increased transiently during the first weeks
post-infarction. p66ShcA knockout mice (KO) were compared to wild type
(n = 82 in total). KO had improved survival and reduced occurrence of
heart rupture post-infarction. Expression of cardiac matrix metalloproteinase 2
(MMP-2) was reduced; fibroblast activation and collagen accumulation were facilitated,
while oxidative stress was attenuated in KO early post-infarction. 6 weeks
post-infarction, reactive fibrosis and left ventricular dilatation were
diminished in KO. p66ShcA regulation of MMP-2 was demonstrated in cultured
fibroblasts: lack or overexpression of p66ShcA in vitro altered expression of
MMP-2. Myocardial infarction induced cardiac p66ShcA. Deletion of p66ShcA
improved early survival, myocardial healing and reduced cardiac fibrosis.
Upon myocardial infarction p66ShcA regulates MMP-2 activation. The role of
p66ShcA in human cardiac disease deserves further study as a potential target
for reducing adverse cardiac remodeling post-infarction.
PMID: 25680868 [PubMed - as supplied by publisher]
[INTERPRETATION: There are things (like p66ShcA) that cause oxidative stress (cell damage by oxidants). Removing those things reduces the oxidative stress and thus improves survival and healing after a heart attack.]
