Ringworm drug for dogs (Fenbendazole) might also cure cancer
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Frisky, so sorry to hear about the disappointing scan results. I hope Navelbine does its job and puts the brakes on any activity. The fact that you feel good right now is definitely important and is an accomplishment in and of itself. I really wish we were seeing shockingly great results with these repurposed drug protocols. Maybe someday, when the protocols are further refined for BC . . . .
On the COC point and whether they can prescribe - they do prescribe and work through one specialty compounding pharmacy. The fixed price is $60 per month total for all four medications. Very inexpensive, considering standard drug/copay prices. I initially thought it was odd that the COC would need to work with a compounding pharmacy unless the pharmacy is putting together the drugs themselves. Not sure exactly what is going on there but the bottles are very generic (white with no brand or generic label). Not clear who actually manufactures the pills from this pharmacy or what the pharmacy is compounding.
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thanks JFL for the loving support and explanation....it makes sense they are using a compounding pharmacy...it's to evade the gouging that we patients would otherwise undergo...so happy to hear that! That means they are getting ready for a long battle...and understand how to get over one of their biggest obstacles...remember pharmaceutical are free to charge whatever they feel like in this country...Bush made that great deal on their behalf
Most of the MBC success stories point toward a much longer treatment period, than the excellent results obtained by Joe in just three months....remember...we have nothing to lose and much to gain...the ultimate freedom from doctors and hospitals...
BevJen I hope you read this update...She was concerned about something I had posted earlier about this...based on another COC participant...
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Dear Frisky, I am so sorry things did not improve but then... why do you feel so well? Do you go with your doctor over scans together? We do not do that at the hospital, so after scans that were showing progression in April 2018, we went with these scans for the second opinion and... the radiologist said after looking at these pictures - I see nothing. Nothing (NED) and progression in same pictures - big difference, isn't it? I know PET is not MRI but still... Do you have a chance to go for an ultrasound of the liver. Good ultrasound specialist can really tell a lot about the situation. I know your list of complementary treatments is huge and you are very knowledgeable about it but I did not notice if you use CBD? I do not want to push you to add another "ingredient" to your cocktail but if something is not working, you might deduct, add, change, reset, start anew. I agree with you we have a lot of to gain and nothing to loose, so true... Hugs, Saulius
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Saulius thank you....you're making some very good points...something is not working...
If I had to take a wild guess I would say it's my diet...although my sugar level are manageable, insulin levels are ignored by doctors...and not tested...the test itself is horrendous because I have to drink large quantities of glucose and have the blood drawn every hour for three hours
I think I have insulin toxicity due to the addiction to wheat, the breads and cheeses I've been eating...and the fresh fruits...I think that's what I have to change first and foremost...get back to vegetables, seaweeds, some proteins, seeds and nuts....and just berries...No panettone for me this Christmas!
Being pain free, however, is not possible when the insulin levels are high...usually there would be swelling, great inflammation, and pain associated with it, so I'm confused.
maybe it's time to find a functional oncologist that can help me figure out what's going on....and what to do next...but if it's not the right one, I'll get frustrated because I'll know more than they do..( like my last one, I had to explain that chromium helps manage sugar levels)
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Mm... changing the diet can be made very quickly (I know it is difficult for some but not for me), and you'll see quickly how you feel too. It is easy to come back to it if something. But also functional (integrative?) doctor would be very good, I too think about one for Sandra...
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as long as your successful, don’t change anything...
There’s no way of knowing what a doctor actually knows...how effective he is...and with cancer timing is of the essence...
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Ok I am sticking to my thoughts on Vitamin E Frisky and let me tell you another reason why. All of our bodies and cancer's react differently than others..and act differently than they would in a mouse...or in a test tube. Last week I spoke to a women on FB Stage 4 cancer who was stable and then did the Vit IVC infusions...her cancer started growing out of control...NOW...they say that IV C at the dose she got through IV is pro oxidative like chemo so it shouldn't have made her cancer wake up and progress ...yet..it did... Does that mean I will not take it...no...but that means that all of our bodies react different and just because taking the E with Joe worked...lets remember Joe DID NOT have Breast Cancer or Hormone Positive breast cancer so what worked for him...in us could be a totally different ball game.
Just my opinion.
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Frisky,
I did see JFL's response.
If you are concerned about your insulin levels, you can have your doc add an A1C test to your bloodwork. It would require a fasting blood sample, but it doesn't require the long glucose test that you are describing. My husband is an insulin dependent diabetic, and that's all his docs use. If you are not familiar with that test, it's just added to the normal blood panel and it provides a 3 month look back as to your insulin levels. You might ask you internist about it, rather than your MO.
Last week, I was away at the beach. Every day, I took long walks, ate healthier, went to aqua fit classes almost every day, and also sat in the sauna a number of times. I felt great every day -- kept checking myself. As soon as I got home and "life" intruded, my stress levels went up, and I started with the aches and pains. I truly think that stress, although it may not cause cancer, plays a part in how we feel. So if you are feeling well, whatever you are doing in your life, keep doing it. You may have cut down on your stress levels, and thus improved your quality of life.
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BevJen, the A1c is what I do get already, but it doesn't measure the amount of insulin circulating only the sugar,
from webMD The A1c measures your average blood sugar -- your doctor may call it blood glucose -- over the past 2 to 3 months. The results tell you how well your diabetes treatment plan is working, or if you have diabetes.
also, my hemoglobin has not been normal for years, because of treatments, so whatever parameters they use to calculate the sugar, I suspect, would have been thrown off anyway....
https://kresserinstitute.com/hemoglobin-a1c-not-reliable-marker/
It would be effective for your husband because he is already under treatment...and takes insulin based on what he eats....
In order to keep sugar and insulin down, ( post-meal blood glucose testing is by far the most reliable and accurate way to determine what's happening with blood sugar, and the most sensitive way of predicting future diabetic complications and heart disease) I've already calculated I can't exceed 20 grams of carbs @ meal...I've gone as far as writing a whole book of recipes ( mostly desserts) based on that premise...
Lately, however, I've been ingesting more like 100 grams per meal...because I was trying to reduce the glutamine, usually found in larger quantities in low-carb diets...since there's no clear way of blocking that pathway...I guess my cancer reverted to sugar...or maybe doesn't care what I eat, it can grow on anything...
Sorry to hear about the stress you've noticed when you returned from a vacation....I try to keep mine to a minimum as well...ashawaganda supports the adrenals that deal with stress...
Nicole, I will look up the research you posted a while back about the vit. E...thanks
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Dear Frisky, I was so upset last night when I read your post. I couldn't even reply. I was close to crying, so I took my nightly pills and went to bed at 730.
I'm so glad that you appear optimistic. The thing is, other MBC patients have found a way to do it. And so can we.
Your in my prayers and my heart Frisky
Sue
adding: And I so agree as long as there is no pain and I can take care of myself I'm ok.
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Thanks Sue, it is what it is..I will continue doing what I've been doing because I believe in it and I have nothing to loose....I just read the pet report, there's progression but it's very minuscule...so I'm glad about that...
Meanwhile, I'm starting to wean off my panini's...just has 3 ounce's of lamb and raw vegetables. Once I get the carbs under control I'll feel even better...
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Frisky I am very sorry about the progression, but happy to hear it is minuscule. So, I am very optimistic the new treatment Navelbine will be a good choice for you. I will fire up many prayers for that intention. I do agree with Santabarbarian that you should look at IV Vitamin C--many, many on the repurposed drug FB forum are doing that. Hopefully you can find someplace nearby you could try that. Perhaps that with the doxycline and azithromycin? From that link I sent earlier that combo looks very promising against stem cells. Lastly, are you doing high dose melatonin? I can't remember. Hugs, J.
Nicole--for that woman who did the IV C that caused her cancer to grow--what kind of cancer did she have and was she doing just that or anything else? That's what gets so hard with all this--I do believe it is the combinations and the types of cancer that impact all the results.
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Around 2008, 2009 I was really interested in vitamin E and breast cancer, and learned about how vitamin E has 8 forms. Of those 8 forms, half are tocopherols and half are tocotrienols. Each of those two groups having 4 subgroups, alpha, beta gamma and delta. Standard vitamin E supplement commonly available is typically purely alpha-tocopherol, which is typically the most abundant of the 8 forms. It's the cheapest as well, and easy to synthesise. Also, in synthesis, made from petrochemicals it is made in a mixture of many stereoisomers (same chemical constituents, but different configurations, like left hand vs right hand), only one of which occurs naturally, the other being purely unknown to nature. So beware of cheap vitamin E. It is highly unnatural. Observational studies showed that people whose diets were rich in vitamin E has lower rates of cancer and heart disease. So, research concentrated on whether persons taking supplemental alpha tocopherol faired better than the average population. The result of the data crunching was that in some cases, persons taking alpha tocopherol supplements faired worse than average. Why was that? Was alpha tocopherol supplementation different from whole spectrum vitamin e found in natural food sources? Research continued on the various 8 constituents of vitamin E and cancer, and in vitro and in vivo animal studies showed that only certain forms of vitamin E acted against cancer, and that pure alpha tocopherol in fact made things worse. Perhaps it disrupted the natural balance of the ratio of vitamin e. The Malaysian Palm Oil Board, who were major proponents of tocotrienols, and have a vested interested in promoting palm oil derived products, conducted a clinical trial on women with ER positive breast cancer. They paired up placebo with tamoxifen, and tocotrienol rich palm oil with tamoxifen head to head. I eagerly awaited the results. Unfortunately, while the group taking the tocotrienols faired better, it was not statistically significant. My conclusion, it would appear that in women with breast cancer, tocotrienol rich vitamin e, at the very least does no harm, and on a statistical basis, it does no good either.
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dang this was hard to get to you---had to copy whole article
Vitamin E and its anticancer effects
Annette Abraham, Ajoe John Kattoor, Tom Saldeen, and Jawahar L. Mehta
Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
ABSTRACT Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, a, b, d, c isoforms of tocopherol and a, b, d, c isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, deltatocopherol and tocotrienol. Unlike alpha-tocopherol, gamma-tocopherol and delta-tocopherol can scavenge reactive nitrogen species in addition to reactive oxygen species. Antiangiogenic effect, inhibition of HMG CoA reductase enzyme and inhibition of NF-jB pathway make the anti-cancer effects of tocotrienols unique compared to other vitamin E isoforms. Preclinical research on nonalpha tocopherol isoforms of vitamin E showed promising data on their anticancer effects. In this review, we deal with the current understanding on the potential mechanisms involved in the anticancer effects of vitamin E and the controversies in this field over last three decades. We also highlight the need to conduct further research on the anticancer effects of non-alpha-tocopherol isoforms in larger population and clinical setting.
KEYWORDS Vitamin E and cancer; tocopherol; tocotrienol; tocopherol and cancer; anticancer mechanisms
Introduction Vitamin E and its anticancer effects is an area of research over last three decades. Multiple trials have been conducted using a-tocopherol, which is a major isoform of vitamin E, to evaluate its anticancer properties, based on the hypothesis that there is intense oxidative stress in many cancers (Jiang 2014). However, large clinical trials with a-tocopherol, a chain-breaking anti-oxidant, did not yield meaningful results. This led to serious consideration of other isoforms of vitamin E, especially c-tocopherol, and tocotrienols. Here, we summarize current understanding of the potential mechanisms involved in the anticancer effects of vitamin E, and the emerging role of tocotrienols.
Structure and sources of vitamin E Vitamin E, a lipid soluble vitamin, was discovered in green leafy vegetables in 1922 (Miyazawa et al. 2009). Vitamin E is a family of 8 natural isoforms, namely, a, b, c, d isoforms of tocopherol and a, b, c, d isoforms of tocotrienol. Tocopherols and tocotrienols have a chromanol ring in common. The 16 carbon hydrophobic phytyl side chain is fully saturated in tocopherols while it has 3 trans double bonds in tocotrienols. Four isoforms each of tocopherols and tocotrienols differ in the degree of methylation and the position of methyl group attached to the chromanol ring (Figure 1) (Meganathan and Fu 2016).
Major dietary sources of vitamin E are nuts and edible vegetable oils. a and c tocopherols constitute 60–70% and 20–25% of consumed vitamin E, respectively. These are mainly found in corn, soybean and peanut oils. Sources of tocotrienols are palm oil, barley and cereal grains (Jiang 2014; Theriault et al. 1999). Until recently, major focus in terms of anti-oxidant use was on a-tocopherol and the role of other isoforms of tocopherols and tocotrienols were dismissed. The absorption and metabolism of tocopherols and tocotrienols takes place via the same pathway. Absorption takes place along with dietary fat and reach peripheral tissues like adipose tissue, skin, muscle, bone marrow via lymphatics. a-tocopherol is protected by a tocopherol transfer protein (a-TTP) in liver and hence is least metabolized (Manor and Morley 2007). The isoforms of vitamin E other than a-tocopherol are catabolized via CYP450 mediated x-hydroxylation or oxidation of side chain, to yield the final metabolite 3'-carboxychromanol or 2'-carboxyethyl-6-hydroxychromans (CEHCs). A portion of vitamin E is metabolized via sulfation. Due to the high affinity of a-TTP for a-tocopherol and x-hydroxylation of other isoforms, a tocopherol has the highest bioavailability (Jiang 2014; Mathur et al. 2015). Tocotrienols, are largely degraded and thus have very low bioavailability (Birringer et al. 2002). Nonetheless, recent work has shown that this low plasma concentration of tocotrienols is sufficient for exerting its therapeutic effects (Meganathan and Fu 2016).
CONTACT Jawahar. L. Mehta mehtajl@uams.edu Medicine and Physiology and Biophysics, Stebbins Chair in Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/bfsn. 2018 Taylor & Francis Group, LLCPossible anticancer effects of vitamin E The relationship between cancer risk and vitamin E has been studied in various epidemiological studies. The anticancer effects of vitamin E has been attributed mainly to its anti-oxidant, antiinflammatory, anti-proliferative, anti-angiogenic, immune modulatory mechanisms and the inhibition of HMG CoA reductase enzyme (Figure 2) (Meganathan and Fu 2016).
Anti-oxidant effect Oxidative stress has been implied in the pathogenesis of various cancers, especially skin and gastrointestinal cancers. All isoforms of vitamin E scavenge reactive oxygen species due to the presence of phenolic hydrogen in their chromanol ring (Jiang 2014). In the human body as well as in experimental animals, free radical chain reactions take place causing lipid peroxidation under oxidative stress. Vitamin E plays an important role in breaking the free radical chain reaction and preventing lipid peroxidation and protecting biological membrane (Burton and Traber 1990; Traber 2007). Nrf2 is a transcription factor that regulates induction of antioxidant enzymes. Vitamin E isoforms, especially c-tocopherol, and to some extent a-tocopherol induce Nrf2 which stimulate gene expression of various antioxidant enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase and phase II detoxifying enzymes (Smolarek and Suh 2011; Smolarek et al. 2013). Among the tocopherol isoforms, c-tocopherol and d-tocopherol are more potent as they have unmethylated C-5 position on chromanol ring. These isoforms can detoxify reactive nitrogen species like NO2 and peroxynitrite by forming 5 nitro-c-tocopherol (Smolarek and Suh 2011). The metabolites of vitamin E like CEHCs also inhibit lipid peroxidation and exhibit a stronger free radical scavenging than vitamin E isoforms. Among the metabolites of vitamin E isoforms, c-tocopheryl quinone is more efficient than a-tocopheryl quinone in oxidant response by increasing levels of glutathione and increasing transcription of activating transcription factor 4 (Ogawa et al. 2008; Cornwell et al. 2002). Due to even distribution of tocotrienols in phospholipid bilayer, they can scavenge lipid peroxyl radicals better than tocopherols (Jiang 2014).
Tocotrienol also exert antioxidant effect by inducing various antioxidant enzymes like SOD and catalase (Aggarwal et al. 2010).
Anti-inflammatory effect All isoforms of vitamin E exert anti-inflammatory action by inhibiting a variety of inflammatory mediators. Isoforms, especially c-tocopherol, d-tocopherol and tocotrienols inhibit cyclooxygenase-2 (COX-2)-mediated production of prostaglandin E2 (PGE2), as well as 5-lipooxygenase (LOX)-mediated production of leukotrienes - LTB4, LTC4, LTD4 (Jiang et al. 2000). The metabolite of vitamin E, 13'-COOH also suppresses COX-2 and LOX pathway (Jiang et al. 2008). Eicosanoids from COX-2 and 5-LOX pathway are known to be involved in colon cancer pathogenesis. Hence, the suppression of these pathways by vitamin E helps in inhibiting inflammation in the colon and carcinogenesis (Ju et al. 2010). Tocotrienols are found to block NF-jB (nuclear factor-kappa
and JAK-STAT3 (Janus kinase-signals transduction and activation of transcription) signaling pathways that mediate expression of various proinflammatory cytokines like IL-1, IL-6, and TNF (Bachawal, Wali, and Sylvester 2010). c-tocotrienol is the most potent vitamin E isoform in this regard. Shibata et al showed that hypoxia inducible factor-1 (HIF-1)-modulated inflammatory pathway is also suppressed by tocotrienols (Shibata et al. 2008). Peroxisome proliferator activated receptors (PPAR-a, c, and d) are ligand mediated transcription factors that modulate inflammatory pathways by inhibiting COX-2. PPARs are also linked with various pathways like PI3k-Akt and NF-jB signaling. In in-vitro and in-vivo studies, d-tocopherol was shown to activate PPARc in various cell lines, suppress inflammation as well as inhibit cell cycle progression and induce apoptosis (Smolarek and Suh 2011; Campbell et al.2003).
Anti-proliferative effect Vitamin E exerts anti-proliferative effect by inducing apoptosis and cell cycle arrest. Apoptosis takes place through extrinsic pathway mediated by death receptor signaling or intrinsic pathway mediated
Figure 1. Chemical structure of vitamin E isoforms.
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by mitochondrial disruption and release of cytochrome c into cytosol. Both pathways finally lead to the activation of execution caspases, especially caspase-3, followed by cleavage of poly-ADP-ribose-polymerase (PARP). Among tocopherols, d-tocopherol and c-tocopherol are more potent than a-tocopherol in induction of apoptosis (Ju et al. 2010). These compounds act mainly via caspase-9 and -3 activation (Ju et al. 2010). Of note, Jiang, Wong, and Ames (2004) identified a caspase-independent mechanism in androgen responsive LNCaP cells; this pathway was inhibited by c-tocopherol (Jiang, Wong, and Ames 2004). Tocotrienols induce apoptosis via different mechanisms involving, death receptor or by increasing Bax/Bcl-2 ratio or activating p53 leading to caspase 9 activation (Park, Sanders, and Kline 2010; Agarwal et al. 2004). Enhanced caspase expression was observed when malignant human liver cells were incubated with various forms of tocotrienols in a dose and time dependent manner (Sakai et al. 2006). Nuclear factor-kappa B (NF-jB) is a major transcription factor involved in cancer pathogenesis. Downstream of this pathway lie Bcl-2 and Bcl-xl, proliferative proteins like cyclin D1 and various angiogenic proteins. Cyclin D1 activation leads to cell cycle progression from G1 to S phase. Tocotrienols inhibit NF-jB signaling pathway resulting in induction of apoptosis and G1 cell cycle arrest (De Silva et al. 2016; Ling et al.2012; Nesaretnam and Meganathan 2011; Wada 2009). Phosphatidylinositol-3-kinase (PI3k)/PI3K-dependent kinase-1 (PDK-1)/Akt signaling pathway is shown to be involved in cancer cell growth and survival. c-tocotrienol was found to block PI3k/PDK-1/Akt mitogenic signaling upstream at the level of epidermal growth factor receptor (EGF-receptor) ErbB3 (Samant and Sylvester 2006). It was shown that, in human breast cancer cell line, d-tocotrienol and a-tocopheryl succinate induce apoptosis by activation of Transforming Growth Factor-b (TGF-b) and Fas apoptotic pathway leading to activation of transcription factor c-Jun and movement of Bax into mitochondria causing release of cytochrome c and apoptosis (Shun et al. 2004).
Anti-angiogenic effect Angiogenesis is a crucial step in growth of tumor as well as tumor metastasis. It involves proliferation and migration of endothelial cells. Inhibition of angiogenesis by vitamin E isoforms especially tocotrienols have been shown in both in vitro and in vivo studies. Among tocotrienols, d isoform is the most potent inhibitor of angiogenesis (Miyazawa et al. 2009; Inokuchi et al. 2003). Other tocopherols do not exhibit this property (Miyazawa et al. 2009). Tocotrienols, invitro in bovine aortic endothelial cells (BAEC) and human umbilical vein endothelial cells (HUVEC) inhibits proliferation, migration and tube formation. Tocotrienols display antiangiogenic property by downregulating vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF) (Aggarwal et al. 2010). In addition, tocotrienols were also found to downregulate VEGF receptor expression. Hypoxia inducible factor (HIF-1) is a transcription factor that activates VEGF expression and result in angiogenesis in response to hypoxia. In a study on human colorectal adenocarcinoma cells by shibata et al, tocotrienol
treatment was found to suppress HIF-1 and thus inhibit secretion of angiogenic factors (Shibata et al. 2008). IL-6 and IL-8 are proangiogenic cytokines that act by upregulating VEGF levels. In HUVEC cells treated with tocotrienols, the levels of IL-6 and IL-8 were found to be lower (Selvaduray et al. 2012). Tocotrienols inhibit phosphorylation of PI3k/AkT signaling pathway and downregulate its signals like endothelial nitric oxide synthase (eNOS), glycogen synthase kinase 3 (GSK3) and extracellular signal regulated kinase (ESRK). This pathway plays a role in angiogenesis by inducing binding of VEGF to its receptor. (Miyazawa et al. 2009). Suppression of angiogenesis is also mediated through matrix metalloproteinase (MMP-9) gene suppression which is essential for tumor invasion and angiogenesis (Liu et al. 2010).
Anti-platelet effect a-tocopherol and c-tocopherol inhibit platelet aggregation. c-tocopherol is more potent than a-tocopherol in this effect (Saldeen, Li, and Mehta 1999). Studies have shown that vitamin E especially a-tocopherol potentiate the antiplatelet effect of aspirin (Gonzalez-Correa et al. 2005). Chang et al, demonstrated that a-tocopherol inhibit platelet aggregation by downregulating Gp-IIb expression in human erythroleukemia cells (Chang, Lin, and Chen 2000). Platelets play a vital role in cancer progression. Platelets protect the circulating tumor cells (CTC) in blood stream by forming platelet clots around them. CTC in turn activate platelets to release various pro-angiogenic factors like vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). Platelets also protect CTC from natural killer-cell recognition, enhancing its survival in blood. Transforming growth factor TGF-b and PDGF released from activated platelets induce epithelial mesenchymal transition (EMT) that aids in cancer cell invasion (Mehta et al. 1987; Leblanc and Peyruchaud 2016). Hence the anti-platelet action of various isoforms of vitamin E is thought to decrease the pro-angiogenic effects of CTCs, enhance CTC recognition by immune cells and negatively influence metastasis.
Inhibition of HMG CoA reductase Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) to lower cholesterol is a property unique to tocotrienols. In certain tumor cells, this enzyme is found to be dysregulated, and metabolites of this pathway contribute to malignant cell proliferation. Tocotrienols, especially c-tocotrienol, lower the activity of HMG-CoA reductase and thus exert anti-tumor effect (Wada, 2009; Parker et al. 1993). Interestingly, a-tocopherol was found to attenuate this activity of tocotrienols when given in combination with other tocopherols (Qureshi et al. 1996). Tocotrienols exhibit synergistic effect with other HMG CoA reductase inhibitors, such as statins (Wali and Sylvester 2007). Wali et al showed that although c-tocotrienol lowered HMG CoA reductase enzyme levels, addition of mevalonate (product of HMG CoA reductase pathway) to the system did not reverse c-tocotrienol-induced apoptosis. This suggests that the anti-tumor activity of tocotrienols may
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2833
not be linked with inhibition of HMG CoA reductase (Wali, Bachawal, and Sylvester 2009). Further studies need to be performed to clarify this link.
Vitamin E and cancer – controversies We evaluated the trends in research in studies on vitamin E and cancer over the last three decades. Studies from 1980s showed an inverse correlation between vitamin E intake and cancer risk. Since tocopherols were known as the potent anti-oxidants and a-tocopherol being the predominant form, this finding was attributed to a-tocopherol. The human case-control and cohort studies that analyzed the relationship between tocopherols and cancer showed inconsistent results (Ju et al. 2010). For example, in Iowa women's health study, there was reduced risk of colorectal cancer with high intake of vitamin E, especially in age under 65years (Bostick et al. 1993). Breast cancer risk was found to be unrelated to the intake of vitamin E, A and C (Kushi et al. 1996). A case-control study on plasma tocopherol and prevalence of colorectal adenoma in multiethnic population showed no protective effect of tocopherol (Ingles et al. 1998). Based on the results of observational studies, various interventional studies were designed to examine in depth the effect of Vitamin E supplementation on cancer risk. The prominent studies and their results are listed in Table 1. The ATBC trial analyzed the effect of a-tocopherol and b-carotene on the incidence of lung cancer and other cancers in male smokers. In this primary prevention trial, there was no association between a-tocopherol and lung cancer, but there was a statistically significant negative correlation
between a-tocopherol levels and incidence of prostate cancer (Cardenas and Ghosh 2013; Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, 1994). Stolzenberg et al was able to show evidence supporting the hypothesis that a higher a-tocopherol concentrations may play a protective role in pancreatic cancer in male smokers (Stolzenberg-Solomon et al. 2009). 18year – follow up of ATBC trial did not show any late effects on cancer incidence with a-tocopherol and beta-carotene. However, the preventive effects on prostate cancer continued resulting in a lower prostate cancer related mortality in the a-tocopherol group (Virtamo et al. 2014). Another groundbreaking interventional study was the SELECT trial which was launched in 427 states across the U.S, Canada and Puerto Rico between 2001 and 2004. It was a randomized double blind placebo controlled trial that looked at the effects of selenium and a-tocopherol on the risk of developing cancer (Lippman et al. 2009). The trial did not find a protective effect of a-tocopherol supplementation but showed a non-significant increase in the risk of prostate cancer risk with a-tocopherol (p¼0.06). In a follow up report, Klein et al reported a significantly increased risk of prostate cancer after vitamin E supplementation (Klein et al. 2011). Kristal et al conducted a survey (Prostate Cancer Prevention Trial) assessing the nutritional risk factors for prostate cancer and concluded that dietary supplementation with vitamin E did not prevent prostate cancer (Kristal et al. 2010). The findings of the interventional studies on Vitamin E and cancer risk were also inconsistent and conflicting (Das Gupta and Suh 2016; Yang et al. 2013). The conflicting results in these studies paved way for the serious
Table 1. Clinical trials evaluating the anti-cancer effects of vitamin E.
Study author, year
Sample size (n), study population Study duration Intervention Results Blot et al. (1993) 29584 adults 5 years Factorial design -Either of the 4 combinations -Zincþretinol or Niacinþriboflavin or Vitamin Cþmolybdenum or a-tocopherolþseleniumþbeta carotene. Significantly lower mortality occurred among vitamin Eþseleniumþbeta carotene group (RR¼0.91; 95% CI 0.640.99, p¼0.03) Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) 29133, male smokers 5–8 years 50mg/day a-Tocopherol Vs. bcarotene 20mg/day Vs. combined Vs. placebo No reduction lung cancer incidence with a-Tocopherol. Decreased prostate cancer in a-Tocopherol group. Lippman et al. (2009) SELECT trial, 32400, men 4–7 years a-tocopheryl acetate Vs. selinium Vs. combined Vs. placebo Non-significant " risk of prostate cancer with vitamin E (HR¼1.13; 99% CI 0.95–1.35, p¼0.06)Gaziano et al. (2009) The Physician's Health Study II 14641 Male physicians in US, >50 yrs 8 years a-tocopherolþVitamin C q.o.d Vs. placebo No difference in incidence of prostate cancer (HR¼0.97; 95% CI, 0.85–1.09, p¼0.58)Springett et al. (2009) 25, Patients with pancreatic ductal neoplasia >18yrs Phase 1 study – 2 weeks d –tocotrienol at escalating doses from 200mg to 3200mg daily given for 13 days before surgery. Significantly increased apoptotic changes and increased caspase 3 levels in intervention group. d –tocotrienol is safe and tolerated well. Nesaretnam et al. (2010) 240, Women, 40-60 yrs, with TNM stage 1 or 2 breast cancer – ERþ 5 years Tocotrienol rich fractionþtamoxifene Vs Placeboþtamoxifene Non significant reduction in mortality by 60% in intervention group (HR¼0.40' 95% CI 0.08–2.05, p¼0.27)Fleshner et al. (2011) 303 Men with High-grade prostatic intraepithelial neoplasia 3 years Vitamin Eþ soyþselenium Vs placebo No reduction in progression to prostate cancer. (HR¼1.03; 95% CI 0.67–1.60, p¼0.88) Study does not mention the type of vitamin E isoform used.
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consideration of other isoforms of tocopherol and tocotrienol. A tocopherol mixture rich in c-tocopherol, c-tocopherol-rich mixture of Tocopherol (c-TmT), displayed a potential in inhibiting cancerous growth in lung, colon, breast and prostate cell lines. c-TmT contains 568mg c-tocopherol, 243 d-tocopherol, 130mg a-tocopherol and 15mg b-tocopherol per gram (Yang et al. 2013). Lu et al (Lu et al. 2010) used A/J mice with chemically induced lung tumors and showed that treatment with 0.3% c-TmT resulted in a significant reduction in tumor multiplicity, tumor volume and tumor burden (30%, 50% and 55% respectively; p<0.05). Further, treatment with c-TmT enhanced apoptotic index (from 0.09% to 0.25%), lowered levels of 8hydroxydeoxyguanine (marker of oxidative DNA damage) and c-H2AX (marker of double stranded break induced DNA repair). The authors also observed reduced microvessel density in the periphery of lung adenoma and decreased plasma levels of prostaglandin E2 and leukotriene B4 in c-TmT treated mice. These findings suggest proapoptotic, antioxidative, antiangiogenic and anti-inflammatory activities of c-TmT in this animal model. These investigators also studied the effect of various isoforms of tocopherol on the growth of H1299 human lung carcinoma cells. They
observed that d-tocopherol and c-tocopherol inhibited cell growth, while a-tocopherol did not, d-tocopherol being the most potent inhibitor. Studies in transgenic rat for prostate adenocarcinoma (TRAP) suggested that c-tocopherol activated caspase-3 and -7 and significantly suppressed progression from prostate intraepithelial neoplasia (PIN) to adenocarcinoma (Takahashi et al. 2009). This potential of c and d tocopherol could be due to their ability to scavenge reactive nitrogen species, a property unique to c and d-tocopherol (Das Gupta and Suh 2016; Yang et al.2013). Further, Akt signaling involved in cancer cell growth was suppressed by c-tocopherol and d -tocopherol. It is possible that higher dose a-tocopherol supplementation would compete with d and c -tocopherols for binding to relevant proteins and decrease the anticancer properties d and c -tocopherols (Das Gupta and Suh 2016; Huang et al. 2013). This may explain the disappointing results of SELECT study. Tocotrienols have not been fully explored in anticancer research, but there are in vitro and in vivo studies in this area (Aggarwal et al. 2010; Wada et al. 2005; Sun et al. 2008). Nesaretnam et al demonstrated that benign breast lumps contained higher tocotrienol (a, c and d-tocotrienol) than the malignant breast lumps, and proposed that tocotrienols may
Figure 2. Postulated mechanisms of anti-cancer effects of vitamin E – 1. Anti-proliferation by cell cycle arrest 2. Antioxidant effect 3. Antiproliferation by inducing apoptosis by promotion of caspase activation and Bcl-2 proteins 4.Anti-angiogenic effect by inhibition of angiogenic factors 5.Anti-platelet effect by inhibiting platelet aggregation.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2835
have a role in scavenging free radicals (Nesaretnam et al. 2007; Nesaretnam 2008). In spite of the accumulating evidence suggesting the potential of tocotrienols as anti-cancer agents, very few clinical trials have so far been conducted on their anticancer effects. A double blinded placebo controlled pilot trial evaluated the effectiveness of tocotrienol combined with tamoxifene in 240 women with early breast cancer showed 60% reduction in mortality (p¼0.27). The major limitation of this study, which was the first experimental study on the use of tocotrienol, was its small sample size and lack of randomization (Nesaretnam et al. 2010). Of note, tocotrienol rich fraction used in the study contained mostly a-tocopherol which might have influenced the results. Springett et al conducted a clinical trial in which d-tocotrienol was given in escalating doses to patients with pancreatic ductal neoplasia for 2weeks before surgery. This study demonstrated significant apoptotic changes as measured by increased caspase-3 levels in patients who received doses 400–1600mg. The authors asserted that d-tocotrienol is a well-tolerated compound with no drug related toxicities with doses up to 1600mg daily. This dose resulted in plasma concentrations that demonstrated bioactivity in preclinical models (Springett et al. 2015). Surprisingly, no major clinical trial has yet fully explored the potential of tocotrienol in cancer.
Recent advances Tocotrienols were found to display a unique property of sensitizing cancer cells to the action of various chemotherapeutic agents (Ling et al. 2012). A combination of c-tocotrienol with ErbB receptor inhibitors like erlotinib was found to be highly effective than monotherapy in inhibiting tumor cell growth in highly malignant mouse mammary epithelial cells (Bachawal, Wali, and Sylvester 2010). Abubakar et al recently showed that combination of c-tocotrienol with jerantinine, an alkaloid with proven anticancer activity, induces potent cytotoxic effects on brain cancer cells (Abubakar et al. 2017). Synergistic effect of c-tocotrienol is seen with a number of chemotherapeutic agents like EGFR tyrosine kinase inhibitors, HMG-CoA reductase inhibitors, cyclooxygenase (COX-2) inhibitor, a Met inhibitor, PPARc antagonists, autophagy inducer, and arylhydrocarbon receptor (AhR) modulator (Wali and Sylvester 2007; Bachawal, Wali, and Sylvester 2010; McAnally et al. 2007; Shirode and Sylvester 2010, Ayoub, Bachawal, and Sylvester 2011, Malaviya and Sylvester 2014; Cui et al. 2007; Yamashita et al. 2016; Eitsuka et al. 2016). In recent years, research on vitamin E has expanded into new realms. Vitamin E isoforms can effectively deliver anticancer agents to target tumor tissue using novel drug delivery systems. Tocopheryl succinate-nanovesicles (TS-NV) were the first ones to be developed. Later, for better stability TS-NV was combined with egg phosphatidyl choline (TSEPC-NV) (Hama et al. 2012). D-a-tocopheryl polyethylene glycolsuccinate (TPGS) which was developed by esterifying a-tocopheryl succinate with polyethylene glycol was found to inhibit growth of prostate and lung cancer cells (Youk et al. 2005). Tocotrienol drug delivery systems include
multilamellar transferrin bearing vesicles encapsulating tocotrienol. They bind to transferrin receptors overexpressed in cancer cells (Fu et al. 2009). The importance of these systems lies in the fact that they result in enhanced uptake into tumor cells and in combination with other chemotherapeutic agents is thought to decrease effective therapeutic dose and limit toxicity. These novel nano carriers are unique in that it has inherent anticancer effect. The efficacy of these systems has been demonstrated in preclinical models.
Conclusion It is clear that studies on c- and d- tocopherol and tocotrienol have provided initial promising data on their anticancer effects. Anti-angiogenic effect, STAT3 activation and inhibition of HMG-CoA reductase enzyme and NF-jB pathway are properties that distinguishes tocotrienol from other isoforms. The accumulating evidence on anticancer properties of tocotrienol in preclinical models warrants future research in clinical settings and larger populations. Recent advances in the realm of vitamin E based nanomedicines for drug delivery needs to be tested in clinical trials. Vitamin E isoforms are very well tolerated natural compounds. Hence fully realizing the anti-cancer potential of them will go a long way in revolutionizing cancer research.
References
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Mysticalcity , unfortunately, the azithromycin is not recommended for people with liver disease....I'm going to continue with the doxycycline and vitamin C, and everything else while looking for a location for the C IV drip...
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and another pdf file on vit e
Vitamin E There is great research by multiple sources that indicate success through Vitamin E ability to interfere with the substances that actually nourish cancerous tumors and help them grow. This interference means tumors can't grow but more importantly can't Metastasize to other body parts. It also thought to be able to induce high rates of cancer cell death without harming surrounding tissues. There is also research to show that Fenbendazole works better in Conjunction with Vitamin E. Joe suggests in his Blog - Tocotrienol and Tocopherol forms (all 8) of Vitamin E (400-800mg per day, 7 days a week). A product called Gamma E by Life Extension or Perfect E are both great. There are numerous studies and in depth literature about the different forms of Vitamin E. Vitamin e Succinate has been mentioned several times on the page.
Here are some links for further information; • http://blog.abhpharma.com/d-alpha-tocopheryl-the-b... • https://www.consumerlab.com/answers/is-the-best-fo... tocopheryl-succinate-as-recommended-by-the-paleo-diet/D-alpha-tocopherylsuccinate/? fbclid=IwAR16cRKtVQq36HizNmpWZG0_ATScMW1lxo4jk3SSOeh0RHlcRKzguvuwLy4
Some of the studies on which Joe based his decision to add Vitamin E into his protocol; 1. https://bmccancer.biomedcentral.com/articles/10.11... fbclid=IwAR1syUDwCfWJ189RRrqJJVXbyGzJWOqlqrw_Mr44DIVlldkgJm-ykvoclK8 2. https://www.researchgate.net/publication/ 260343692_Effects_of_fenbendazole_and_vitamin_E_succinate_on_the_growth_and_survival_of_pro state_cancer_cells?fbclid=IwAR0cZniUH3yu_CJZzQFy4xscfFWThUCQGM3jS5DPhvF3ZCFOLz7b6ioaUU 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC26871... fbclid=IwAR0cZniUH3yu_CJZzQFy4xscfFWThUCQGM3jS5DPhvF3ZC-FOLz7b6ioaUU0 -
Omg, Sue, God bless you...everything we want to know about the results of every vitamin E study is right there! Will copy and paste this info in my notes. I do have the life extension Gamma E and curcumin as specified. Thanks again.
You are all magnificent, my dear friends, I'm just grateful and overwhelmed by your love and support...
It’s amazing how much carbs affect me, it’s one pm here and I’m not the least hungry...I can’t even think about food...even my mother’s Tiramisu wouldn’t get me excited....
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Snooky, that is a great article summarizing the research on vitamin E to date. It is encouraging to know that actual interventional studies on women with breast cancer that showed either no harm or potential benefit. That goes well beyond the theoretical, in vitro or even animal studies. Its just a pity that the Malaysian study didn't have enough power (ie number of participants) to yield statistical significance. It would have been game changing had it been larger or the results more dramatic.
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Frisky it sounds like you may be insulin resistant due to diet. That could be thwarting you.
To to break the addiction to carbs, you might try a ketogenic diet for a few weeks, but NOT the "Atkins" version with a ton of meat and cheese. More of a "whole foods vegan/pescatarian" diet with veggies seeds, nuts, avocado, and if you want, deep sea fish. Limited Omega 3 Eggs ok. Limit fruit and legumes, initially. You can do 1/2 C berries, a green banana or a green apple per day, OR a 1/2 C of beans, lentils, etc. Only one "carby" food (must be nutrient dense). So initially, you are getting more like 35-45 carbs per DAY on this "induction" plan.
Once you are in ketosis you can gradually bring the fruits and legumes back in, noting your ketones and figuring out how many carbs can keep you on the edge of ketosis/ mild # of ketones. he Dr Block recommended diet has NO refined carbs-- zero white flour, sugar, potato, white rice-- and NO high-glycemic-index foods.
Keto can feel horrible for 2-3 weeks while you adjust; you can get brain fog or headache-- which I think can mean yeasts dying off-- but you won't feel hungry -- because you can have unlimited amounts of the low carb foods.
I did Keto as well as fasting mimicking diet (another form of getting into ketosis quickly) to deal w my glucose pathway.
One other thing that can really help with insulin insensitivity as well as immune system performance is intermittent fasting. Make sure you have 13 hours of NOT eating between dinner and you morning meal. Changed my digestion and my weight a lot just to have a window of not eating slightly larger than my window of eating....
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thanks Santa, I totally agree with your program...I started this morning, going cold turkey with the lamb and vegetables, it made me feel so full, I just had another two bites of lamb and I can't even think about eating again...
Will switch out of the meat, but I needed something that I knew would kill my appetite and cravings immediately....will use all your suggestions, I'm very familiar with the process....XXXOOO
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Hi Ladies,
My wife has been taking FZ with Vitamin E, Curcumin and CBD oil for 3 weeks.
her first blood test was just done and found that her neutrophils is lower than before. I understand one of main side effect of Ibrane is low neutrophils but has anyone of you whom take FZ experienced low neutrophils?
She said she read somewhere that FZ can lower neutrophils.. I could not find anything like that including this tread.
Thanks!
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My wife has been taking the FZ 3 on 4 off for 12 plus weeks prior to getting her latest blood test. She is on Ibrance / Letrozole and always has low neutrophils. Commonly lower than 1.0 at the end of her cycle. Her latest neutrophil test wasn't any lower than her average low. So, its hard to say if the FZ had any negative impact.
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Never heard of that problem associated with FZ...in fact there are no problems due to the incredibly low amounts to be taken..
Maybe someone else will know differently....good luck with the protocol and keep us posted please
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***I am going to be posting some info in the Jane thread about IVC and Doxy etc...I don't want to put it here because this is Joes Protocol...not janes...so If you want to check it out please do
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here is a positive from FB joes page...I am only posting it here because it is about fenben...
Awesome story!!!
A friend of mine has inflammatory breast cancer, and has been with an oncologist out of Nevada for the last six years. It's been a long haul. This past year she was on oral chemo drugs and was supposed to return to Reno for her follow up in October. BUT!!!! Her oncologist called her in summer and told her to quit the chemo and order fenbendazole online, start it, and only come back for follow up once the tumour was gone. Whaaaat??!?!
The tumour had been the size of a hockey puck in diameter and thickness when he called. She started the fenbendazole and as of now it's shrunk over 30% (by feel). Listen you guys!!! Her oncologist has had so much success that he literally EXPECTS her to have no tumour as she continues this!
I found this super exciting and encouraging. Hope it cheers you on in your journey to health as well. ♥️
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Interesting post. Honestly, I hope it is true but it sounds a bit like the truth may have been stretched. Apologies, I have no basis to say either way but my gut tells me that sounds off - not that her tumor shrunk, that is believable - but that her MO told her to stop chemo, start taking fenben and not to call him until the tumor is gone. Something not adding up there.
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totally second JFL, no oncologist on this planet would be caught dead saying that....just not possible....therefore the post comes from someone inexperienced in these matters
if there was a second coming of Christ, doctors would need 20 years of clinical trials...before cautiously admitting anything, and than the FDA would insist it was quackery all along...
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Frisky and JFL When I first read that post a few days ago I was so excited. But then common sense entered. I agree with everything you said. I believe an Onc would possibly lose his license for going that far away from standard of care. And he's long distance from his patient. I didn't read the comments to this post, think I'll go back and do that.
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MY Surgeon's office has their pens in a coffee cup on the counter in the front office... the cup says "Please don't confuse your Google search with my medical degree." Which, though I am an inveterate Googler, gave me a chuckle...
We need to search for ideas or trials that are not (yet) standard of care but have huge promise if we want or need an innovative approach to our disease. That is intelligent and forward thinking, But then we need to have medically knowledgeable people help us implement (or reject) the ideas we find. I am pretty shocked at how people buy into anonymous internet strangers' advice. You cannot project anything about your own response to a drug from someone else's good or bad response. There are too many variables. ER, PR, AR, grade, chronic conditions, diet etc.
When a person posts about a bad outcome on fenben or COC, it's very hard to know how advanced that person's disease might have been before attempting it. Or whether they have underlying issues that affected the treatment. Once the level of disease is extensive the same drug will have a much harder battle.
Again, anyone wanting deep, scientifically-valid knowledge of integrative practices for cancer should consult the appropriate expert. No matter how intelligent/helpful a given approach might be, there is always someone saying the opposite (whether they know what they are talking about or not!).
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Santa what you state makes lots of sense until you look at the results and statistics of ALL that medical knowledge....
I think, a lot of people with terminal diseases, such as Jane Mc Lelland, are forced to try to figure things out on their own because 2% survival rate is something no one would or should be proud of...or trust!
Don't confuse the successful rates of patients in the early stages, with stage 4. Also the 30% rate of progression to stage four, tells me, that those medications can't even protect those relatively healthy people...therefore the lack of trust...
I sincerely wish reality was different...but yes!, I agree that people should avail themselves of whatever knowledge doctors have, unless you're a Jane Mc Lelland type that can advance research in the opposite direction of the failing business models of the business as usual protocols...
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