Colorectal Cancer (CRC), in the US alone, is expected to kill approximately 52,550 people in 2023. Keep in mind that many of these deaths will have been treated with standard CRC therapy, yet they still die :
Here is a relevant quote from the article :
' In the United States, colorectal cancer is the third leading cause of cancer-related deaths in both men and women, and it's the second most common cause of cancer deaths when numbers for men and women are combined. It's expected to cause about 52,550 deaths during 2023. '
So the above article clearly shows the severity of CRC in the US as well as a less than optimal outcome for many with CRC.
I will start out by linking to an article that clearly gives a basic understanding of CRC that is easy to read and understand and allows you to select specific categories of CRC that you may be particularly interested in :
https://www.cdc.gov/cancer/colorectal/basic_info/index.htm
I want to concentrate more on six supplements that have shown benefit in studies of CRC. These studies are mainly animal studies or in vitro studies and are given in no particular order. Some of the studies show that some of these supplements have synergy with standard care for CRC, which is going to be very important for most people who have CRC.
Please note that the above information provided here is solely intended for informational purposes and cannot replace the need for proper medical attention from a qualified healthcare professional, such as an oncologist or healthcare provider. It is highly recommended to seek advice and direction from your doctor in case of a serious condition such as Colorectal Cancer.
Berberine
The first supplement I would like to discuss is Berberine which has shown multiple methods of action in fighting CRC. This first review of previous studies gives a good example of some of the effects that berberine has shown against CRC :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096113/
Here is a relevant quote from the review :
' In this review, we herein offer beneficial evidence for the utilization of BBR in the management and treatment of CRC, and describe the underlying mechanism(s). The review emphasizes several therapeutic effects of BBR and confirms that BBR could suppress CRC by modulating gene expression, the cell cycle, the inflammatory response, oxidative stress, and several signaling pathways. In addition, BBR also displays antitumor effects in CRC by regulating the gut microbiota and mucosal barrier function. This review emphasizes BBR as a potentially effective and safe drug for CRC therapy. '
In the next study mice who have colitis associated cancer (CAC) are treated with Berberine to good effect. CAC is one form of CRC and this study is very interesting because it shows other methods of action of berberine via manipulation of the gut microbiome and causal increase of 3 predominant short chain fatty acids (SCFAs) that have shown health benefits in many other studies and these three SCFAs include butyrate one of the more healthful proven SCFAs :
https://pubmed.ncbi.nlm.nih.gov/35660350/
Here is a relevant study quote :
' Our study showed that berberine alleviated the colitis-associated colorectal tumorigenesis from three equilibrium levels: (1) Pathogenic and beneficial bacteria; (2) Short-chain fatty acids and LPS produced by intestinal flora; and (3) Inflammatory cancer transformation signaling and intestinal barrier function. This study provided a new approach and experimental basis for the application of berberine in the treatment of CAC in clinical practice. '
Zinc
This Next study shows that Zinc has synergy with Berberine in fighting CRC :
https://pubmed.ncbi.nlm.nih.gov/36394793/
Here is a relevant study quote :
' Our findings showed that the combination of zinc and berberine has synergistic anti-cancer efficacy and thus could be used as a potential chemopreventive option for colon cancer. '
One harsh reality of chemotherapy is the fatigue it can cause and I have seen this firsthand and it can be very rough, especially during a very difficult time that CRC is. The following study shows zinc supplementation can prevent the fatigue and improve quality of life :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433302/
Here is a relevant study quote :
' This study showed that oral zinc supplementation 45 days before, and up to 12 weeks after chemotherapy for colorectal cancer, prevents worsening of fatigue symptoms and preserves quality of life. The reduction in the Placebo Group score indicates relevant worsening of fatigue, considering that the minimal clinically important differences for the fatigue scale is 3.0 points. '
Benfotiamine
Benfotiamine is a fat-soluble form of vitamin B1 that is significantly better absorbed than the water soluble vitamin B1 Thiamine Hydrochloride. This first study illustrates how benfotiamine can be more effective than thiamine hydrochloride and another fat soluble form of vitamin B1, Sulbutiamine in the fight against cancer :
https://www.sciencedirect.com/science/article/pii/S0753332219352709
Here is a relevant study quote :
' Pharmacologic administration of benfotiamine, but not sulbutiamine, reduced tumor growth in a subcutaneous xenograft mouse model. '
This second study is an in vitro study and illustrates the beneficial effects of benfotiamine against CRC :
Here is a relevant study quote :
' We therefore investigated the role of benfotiamine in the prevention of carcinogenic signals leading to CRC in cell culture as well as murine models of CRC. Our results show that treatment of human colon cancer cells (HT-29 and Caco-2) in culture with benfotiamine prevented the cancer cell proliferation. Further, benfotiamine also prevented the growth of human adenocarcinoma cells (SW480) -induced tumor growth in nude mice xenografts. Our studies also indicate that benfotiamine prevented NF-kB-dependent survival signals and activated caspase-3 dependent apoptotic signals in colon cancer cells. Further, benfotiamine supplementation also suppressed azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation in mice and AOM-induced inflammatory changes such as activation of Cox-2 and iNOS, and carcinogenic changes such as expression of cyclin D1 and β-catenin in mice colons. In conclusion, our results indicate that benfotiamine prevents colon cancer cell growth in culture and nude mice xenografts as well as formation of ACF in AOM-treated mice. Thus benfotiamine supplementation could be used as an excellent chemopreventive agent for the treatment of CRC. '
One of the known side effects of certain chemotherapies and possibly radiotherapy is neuropathy and Benfotiamine has shown benefit in humans in treating peripheral neuropathy. The following study discusses this aspect of Benfotiamine :
Here is a relevant quote :
' Studies have shown that benfotiamine improves neuropathy scores significantly,301,302 increases nerve conduction velocity,303-305 and reduces HbA1c and pain.306
Vitamin D
Vitamin D has many beneficial health effects and many people have levels that are either insufficient or deficient. The following article suggests that higher vitamin D levels may have preventative effects against CRC. So getting your 25 OH d level into the upper half of the reference range seems like a safe relatively easy thing to do to try and getting CRC in the first place :
Here is a relevant quote from the review : This next
' This review aims to shine a light on the influence of vitamin D over CRC and to further understand its ability to be used as a potential economical treatment for CRC patients. For this review, PubMed was used as the main database for the literature search. Studies on the role of vitamin D on CRC within 10 years and all of the study types were included. Post the extensive research over PubMed, it was noted that vitamin D, through its effect on multiple pathways, especially Wnt/β-catenin, apoptosis, and inflammation, hinders the progression of CRC carcinogenesis. High levels of this steroid hormone can delay the progression and may provide a cost-effective way of treating CRC patients. '
This next human study examining vitamin D levels shows clearly that higher vitamin D levels reduced the incidence of CRC as well as the death rate in people with CRC with higher levels of vitamin D having the best effect :
https://onlinelibrary.wiley.com/doi/10.1002/ijc.33580
Here is a relevant study quote :
' We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1-SD increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC. 'This is a very good case for getting your (25 ) OH d level into the upper half of the reference range. The reference range is 30~100 ng/ml.
Melatonin
Melatonin has multiple effects against multiple forms of cancer including CRC. The following study highlights some of these effects and also mentions a little bit about melatonin's therapeutic role in the gut microbiome as well as how it synergizes with both chemotherapy and radiotherapy to reduce CRC :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798083/
Here is a relevant quote from this review :
' Mechanically, it has been reported that melatonin prevent and delay the progression of CRC by suppressing the proliferation and inducing apoptosis of CRC cells. Ji et al. demonstrated that melatonin regulated the miR-34a/449a cluster, thus influencing the cell cycle in CRC . Yun et al. noted that melatonin promoted CRC cell apoptosis via superoxide-mediated ER stress . Besides, melatonin promotes chemotherapeutic drug-mediated apoptosis of CRC cells by enhancing oxidative stress . In addition to its role in sensitivity to chemotherapeutic agents, melatonin also sensitizes human CRC cells to γ-ray ionizing radiation both in vitro and in vivo. Interestingly, studies have pointed out that melatonin plays a preventive and therapeutic role in CRC by regulating lipid metabolism and gut microbiota . '
This next study is interesting because it suggests that an alternating treatment using Paclitaxel (PTX) and melatonin (MTN) one after the other may be more effective than either one alone against CRC, a relatively new concept :
https://pubmed.ncbi.nlm.nih.gov/36063977/
Here is a relevant quote from the study :
' The present study suggests that sequential treatment with MTN and PTX distinctly affect apoptosis and cytotoxicity via regulating mTOR and MAPK pathways differentially in CRC. '
This next review is fairly new (February 2023) and suggests that melatonin synergizes with one of the most widely used treatments in cancer therapy, 5-fluorouracil. It also discusses how melatonin reduces drug resistance antineoplastic and chemo agents, a common reason for failure of chemotherapeutics to reach the desired goal :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912526/
Here is a relevant quote from the review :
' The combination treatment of 5FU with melatonin in both in vitro and in vivo cancer models increases the hope for a brighter future for the common use of combined chemotherapies. Overall, melatonin in combination with 5FU as a chemotherapy drug may improve its clinical application in cancer treatment and play a significant role as an adjunct for a variety of different tumors . '
Piperine
Piperine comes from black pepper and has multiple beneficial health effects although it is mainly known for increasing the bioavailability of supplements that have poor bioavailability such as curcumin. Piperine also has anticancer effects and improves the bioavailability of many chemotherapeutic agents as well as improving resistance to radiotherapy as discussed here :
Here is a relevant quote from the review that shows just how multifaceted piperine is when it comes to treating cancer of multiple types :
' Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC) self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp) and has a significant effect on the drug metabolizing enzyme (DME) system. Because of its inhibitory influence on P-gp activity, piperine can reverse multidrug resistance (MDR) in cancer cells and acts as bioavailability enhancer for many chemotherapeutic agents. In this article, we emphasize the potential of piperine as a promising cancer chemopreventive agent and the knowledge we collected in this review can be applied in the strategic design of future researches particularly human intervention trials with piperine. '
More specifically, this next study(September 2020) shows how piperine works against CRC in rats :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565681/
Here is a relevant study quote :
' We found that piperine inhibited NF-κB by the activation of Nrf-2, blocking downstream inflammatory mediators/cytokines (TNF-α, IL-6, IL-1β, Cox-2, PGE-2, iNOS, NO, MPO), triggering an antioxidant response machinery (HO-1, NQO-1, GSH, GR, GPx, CAT, SOD), scavenging ROS, and decreasing lipid peroxidation. Histological findings further validated our molecular findings. It also downregulates CEA, MDF and ACF, markers of precancerous lesions in colon, alleviates infiltration of mast cells and depletes the mucous layer. Our results indicate that piperine may be an effective molecule for the prophylactic treatment of colon carcinogenesis by targeting the NF-κB/Nrf-2/Keap-1/HO-1 pathway as a progressive strategy in the preclusion and effective treatment of colorectal cancer. '
So when you consider how piperine works against cancer by itself and then combine its synergistic effects with chemotherapy and radiotherapy, you can start to see how it can be quite useful in fighting CRC.
Conclusion
So these 6 supplements show anti CRC activity as well as synergy with standard therapy and they have very good safety profiles that is probably significantly better than any drugs used against CRC. Some of them also help protect against the negative side effects of standard CRC therapy which should result in improved quality of life during and after treatment. Recent studies confirm their synergistic activities with standard therapy making them attractive as adjunctive additions against CRC. Some oncologists will consider some of these supplements or possibly all of these supplements as part of a treatment plan and I would guess vitamin D and melatonin would be near the top of the list because of studies that clearly support their use. Newer studies with berberine are likely to put it higher on the list also. One important consideration is the safety profiles of these 6 supplements which are very good.
1. Berberine
2. Zinc
3. Benfotiamine
4. Vitamin D
5. Melatonin
6. Piperine
Lastly, there are many other supplements or medications that have activity against CRC, but they mostly have even more limited studies to support their use. Some examples would be Ivermectin, Mebendazole and Albendazole. They look promising, but the studies aren't quite robust enough yet, but there are some anecdotal reports that suggest significant activity against various cancers. The current studies seem to mainly suggest that they can reduce drug resistance to chemotherapy and radiotherapy similarly to the supplements above, but future studies should reveal more of their methods of action.
Silver Nanoparticles (Colloidal Silver)
I would like to discuss one other supplement that I am not putting on the list because I think few if any oncologists would consider adding it to a treatment regimen. That supplement is silver nanoparticles (AgNPs) which also has shown potent anticancer activity while displaying minimal toxicity to normal cells in multiple studies. Here is a study (June 2022) discussing the effects of AgNPs on pancreatic cancer just as an example on the multiple anticancer effects of AgNPs :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797005/
Here are some relevant study quotes :
' Pancreatic ductal adenocarcinoma, with the high resistance to chemotherapeutic agents, remains the fourth leading cause of cancer-death in the world. Due to the wide range of biological activity and unique properties, silver nanoparticles (AgNPs) are indicated as agents with potential to overcome barriers involved in chemotherapy failure. Therefore, in our study we decided to assess the ability of AgNPs to kill pancreatic cancer cells, and then to identify the molecular mechanism underlying this effect. Moreover, we evaluated the cytotoxicity of AgNPs against non-tumor cell of the same tissue (hTERT-HPNE cells) for comparison. Our results indicated that AgNPs with size of 2.6 and 18 nm decreased viability, proliferation and caused death of pancreatic cancer cells in a size- and concentration-dependent manner. Ultrastructural analysis identified that cellular uptake of AgNPs resulted in apoptosis, autophagy, necroptosis and mitotic catastrophe. These alterations were associated with increased pro-apoptotic protein Bax and decreased level of anti-apoptotic protein Bcl-2. Moreover, AgNPs significantly elevated the level of tumor suppressor p53 protein as well as necroptosis- and autophagy-related proteins: RIP-1, RIP-3, MLKL and LC3-II, respectively. '
In addition, we found that PANC-1 cells were more vulnerable to AgNPs-induced cytotoxicity compared to pancreatic non-tumor cells.
' In conclusion, AgNPs by inducing mixed type of programmed cell death in PANC-1 cells, could provide a new therapeutic strategy to overcome chemoresistance in one of the deadliest human cancer. '
To me this gives a good idea of just how cytotoxic AgNPs are to deadly pancreatic cancer cells while not being nearly as toxic to normal cells and similar activity has been shown in other types of cancer. I have used AgNPs for many years and have experimented with doses high enough to kill cancer and it has shown little if any side effects. So AgNPs are on my radar for treatment of multiple forms of cancer and I can't wait for more studies to fully elucidate proper dosing in human studies.
Art
Please note that the above information provided here is solely intended for informational purposes and cannot replace the need for proper medical attention from a qualified healthcare professional, such as an oncologist or healthcare provider. It is highly recommended to seek advice and direction from your doctor in case of a serious condition such as Colorectal Cancer.
