Can Intravenous Vitamin C and Fast Mimicking Diet Shrink Tumors?
Ascorbic acid, or ascorbate, is a soluble in water that is necessary for human physiology. Several of its physiological activities are dependent on its capacity to work as an antioxidant or a cofactor. It works as cofactor, absorbs iron and produce various hormones. Over the past two decades, high-dose IVC has reemerged as an effective anti-cancer agent. Several phases I and a small number of phase 2 clinical studies have reported high safety and tolerance along with encouraging signs with monotherapy and combination therapy for efficient treatment of various cancer types. Additionally, IV vitamin C has been shown via strong clinical research to improve palliative care patients’ quality of life and minimize chemo-related side effects including lethargy.
Researchers from USC and the IFOM Cancer Institute in Milan have discovered that adding vitamin C to a fasting-like diet may help cure some cancers more successfully. In numerous animal trials, scientists discovered that the combination slowed tumor growth in different colorectal cancer mouse models, and in some mice, it led to disease remission. The Nature Communications publication published the findings. The findings offered hints as to why earlier investigations into vitamin C as a potential anticancer treatment had minimal success. Vitamin C treatment in cancer and increasing ferritin protein (which binds to iron) is another approach for KRAS mutated cells to defend cancer cells. But the researchers were able to make vitamin C more hazardous to cancer cells by lowering ferritin levels. The researchers also found that colorectal cancer patients have a decreased likelihood of surviving when their iron-binding protein levels are high. Currently, the effects of fasting-like diets combined with various cancer-fighting medications are being studied in at least five clinical trials, one of which is being conducted at USC on breast cancer and prostate patients [1].
Numerous research using pre-clinical cancer models have found promising anti-cancerous effects of vitamin C at mM doses of 1–20 mM. Leukemia, colon cancer, melanoma, pancreatic cancer, and prostate cancer have received the most research attention. With these similar outcomes many cases of cancer are treated such as breast, thyroid , non-small cell lung, ovarian cancer, hepatocellular carcinoma, malignant mesothelioma, neuroblastoma, squamous cell carcinoma and glioma.
The effectiveness of VitC monotherapy with high-dose (1.25 g/kg) in respectable or , pancreatic, lung cancers and metastatic colorectal is currently being investigated in phase II research. The purpose of the trial (NCT03146962) is to examine the tumor response in BRAF or KRAS mutant metastatic cancers and to investigate the impact on the pathological responses in respectable tumors [2]. Additionally, many oral (NCT03682029) and monotherapy of low dose (NCT03613727) studies in tumors (non-solid) are now proceeding following the encouraging pre-clinical evidence about these latter cancer types (NCT04046094, NCT03682029) [3].
For instance, recent, multicenter, epidemiological regiment research revealed improvement in appetite, weariness, sleep and depression disturbances in breast cancer and terminal patients of breast cancer who got complimentary 7.5 g IVC in addition to receiving the appropriate conventional regimens [4]. A single-center, single-blind and parallel group study conducted more recently in patients with breast cancer revealed a similar and ameliorating improvement in symptoms such as nausea, exhaustion, pain due to tumor, and appetite loss when given 25 g of IV Vit C once a week in addition to the patients’ current standard care. Fortunately, once the IVC treatment began there were no signs of toxicity [5].
Wang et al. used a combination of IV Vit C (1.5 g/kg) with FOLFIRI with or without bevacizumab once a day for 3-14 days cycle. The treatment was continued before disease progression uncontrolled toxic effects with 12 cycles [6]. Potential therapeutic efficacy was noted in addition to a favorable safety profile in 24 patients, when disease control rate is monitored 14/24 patients demonstrated ORR of 58.3% and 4 out of 9 patients showed SD and ORR of 37.5%. They also find similar efficacy in patients with mutant and wild type RAS and BRAF malignancies. This project has recently been expanded into a random trial (phase 3), with an anticipated enrollment of 400 patients, inspired by these encouraging outcomes (NCT04516681). This is the only phase 3 experiment that has looked at high-dose IVC as a cancer treatment to date [7].
In one randomized phase II trial, individuals with advanced-stage NSCLC were evaluated between BSC alone and BSC plus high-dose IV Vit C with modulated electro hyperthermia. For the patients with advanced NSCLC, this combination of treatment is non-toxic, along with the quality of life. The overall results showed that it is less toxic [8].
It has been demonstrated that melphalan and arsenic trioxide, which is an active treatment for multiple myeloma, work together synergistically both in vivo and invitro. Using a combination of IV ascorbic acid (AA), melphalan, and arsenic trioxide as preparation for treatment in patients receiving a very high dose and hematopoietic progenitor cell transplantation (autologous) for multiple myeloma, researchers conducted a phase 1 and 2 trial to assess its safety and effectiveness. We also evaluated the effect of ATO concentrations on the PK, engraftment, and toxicity of melphalan. 25 secretory myeloma patients received treatment. During treatment on day 3 and 4, all patients got Vit C 1000 mg/day and melphalan 100 mg/m2 IV. Arsenic trioxide is a safe and well-tolerated preparation when administered with melphalan and ascorbic acid. Treatment with Vit C resulted in reduction of tumor size [9].
In cases of acute myeloid leukemia and myelodysplastic, Welch et al. undertook a phase 1 research to evaluate the effectiveness and safety for combination of Vit C, arsenic trioxide, and decitabine. Decitabine (20 mg) once a day was administered to patients in fixed doses five days every month, along with IV Vit C (1,000 mg after arsenic trioxide). After enrolling 13 patients, they determined that 0.2 mg/kg dose of arsenic in conjunction with Vit C and decitabine was the highest dose that could be tolerated. At the end of the study, they concluded that 5 patients had stable disease, and 1 had incomplete blood count recovery. We assessed this therapy’s impact on angiogenesis in vivo. Unexpectedly, they noticed a rise in micro vessel density after two cycles with no discernible impact on the production of angiogenic mRNA. Based on these findings, a dose combination of Vit C, arsenic trioxide, and decitabine is suitable for Phase 2 investigations. Volume and size of the tumor were both decreased [10].
Fasting Mimicking Diet (FMD)
The effects of fasting on cellular protection, ageing, and disease have been the subject of extensive study by Longo. His theory is that fasting may play a role in promoting a long, healthy lifespan because the genes and mechanisms that regulate longevity are conserved across all organisms.
As such, the FMD is a 5-day dietary protocol that provides the body with essential nutrients while also being low in total calories, protein, and sugar. It is hypothesised that the body enters a semi-fasted state when caloric intake is drastically reduced, typically by 34% to 54% of the normal caloric intake
The FMD is thought to have some of the advantages of long-term water-only fasting without the dangers.
Fasting has been linked with a number of health benefits, few of that will be discussed later in the article:
• Diminution of Body Mass
• Vitality of the Heart
• Enhanced glucose tolerance
• Assistance with cancer treatment
Calories Consumed While Imitating a Fast
Throughout the 5-day period, this is the typical recommended caloric intake:
1,090 calories (or 10% protein, 56% fat, and 34% carbohydrates) for day 1.
Calories for days 2-5 equal 725 (9 percent protein, 44 percent fat, 47 percent carbohydrates).
The Fast Metabolism Diet is not meant to be followed for an extended period of time.
Patients who are morbidly obese and want to lose weight for health reasons (or to manage chronic health conditions) should have it done monthly, while those who are health-conscious and want to live longer should have it done twice or three times a year.
You should discuss to a doctor to see if the FMD is safe for you to try if you’re curious about trying it.
What can you eat while on an FMD?
The FMD emphasises consuming low-protein and low-sugar whole foods.
What you can expect from a typical day of eating on the FMD:
- Herbal tea and a nut butter bar for breakfast.
- Soup and kale crackers for a light lunch.
- Snack: An olive or two
- Dinner is a bowl of soup again.
- Multivitamin + supplemental DHA
If anyone is a good candidate for the FMD, who are they?
The goals of the Fasting Mimicking Diet are to:
• People who have high body mass index (BMI) and are hoping to reduce their fat percentage.
• Those who want to keep eyes on their health and maybe even extend their lifespan.
• Those who are suffering from certain long-term health issues (although approval from a medical professional is needed)
It should be noted that the FMD is not an appropriate choice for:
1) Women who are expecting or nursing.
2) Children.
3) Anybody who has ever struggled with an eating disorder.
4) Those who have certain medical conditions (unless given the all-clear by a doctor) should not participate.
What Can You Expect from a Fast-Imitating Diet Lasting 5 Days?
The ProLon website lists the following physical changes that occur throughout a 5-day FMD:
Day 1: the body begins to enter a fasted state, increasing fat burning and priming the cellular cleanup process.
Day 2: you’ll notice an increase in fat burning and a better cell cleaning process (autophagy) functioning.
Day 3: participants keep clearing out their cells and many enter ketosis, switching to using stored fat for energy instead of glucose.
Day 4: Continued fat burning and cellular cleaning.
Day 5: you will have finished your fast, and the food you eat from here on out should “fuel your overall wellness.”
If FMD works, what are the possible advantages?
1. Aids in Weight Loss and Decreases Stomach Fat
Dr. Longo conducted a small study in which those who followed three cycles of the ProLon Fasting Mimicking Diet saw greater weight loss and a smaller percentage of abdominal fat than the control group.
While these findings are promising, it is important to keep in mind that they do not prove that the FMD is superior to either calorie restriction or a traditional Ketogenic diet in terms of weight loss.
2. Potentially Better Markers of Cardiovascular Health
Throughout the same study, participants’ blood pressure and cholesterol levels improved across all three FMD cycles. This was especially true for those who began at a higher level. [*]
Since cardiovascular disease & stroke are the leading causes of death[*] worldwide, these developments may be promising if further studied.
3. Helps to maintain normal blood sugar levels.
Presently, diabetes affects an estimated 415 million (1 in 11) people worldwide, and this number is expected to rise to 642 million by 2040.
Preliminary studies have shown promise for a beneficial role for the FMD in diabetes. In the ProLon study, participants whose blood sugar levels were initially elevated saw their readings return to normal.
The regeneration of pancreatic -cells, which produce insulin, has also shown promise. Mice with T1D or T2D have been rescued from their disease by undergoing FMD cycles, which has been shown to restore -cell function. Regeneration of beta cells was also found in the pancreatic cells of humans with Type 1 diabetes in the same study.
4. Could Aid Cancer Treatment
Research has shown that the FMD may be useful in the treatment of cancer, and these findings have been met with cautious optimism.
It has been suggested that the FMD can be as effective as water-only fasting in making breast cancer tumors more susceptible to chemotherapy.
FMD cycles have been shown to improve cognitive performance and reduce cancer risk in mice in animal studies.
5. It has the potential to lessen inflammation and aid in the treatment of autoimmune disorders.
Research conducted in 2016 showed that FMD decreased pro-inflammatory cytokines, increased corticosterone levels, and suppressed autoimmunity.
From their findings, the researchers determined:
Patients with relapsing-remitting multiple sclerosis (RRMS) might benefit from a chronic ketogenic diet or a functional medicine diet (FMD).
Another study found that by undergoing a series of 4-day FMD cycles, the gut microbiome could be modulated and intestinal regeneration could be facilitated, resulting in a decrease in inflammatory bowel disease pathology.
Animal tests also showed that FMD helped revive the immune system.
6. Could Promote Health-span
Increased autophagy in nerve cells has been observed in mice undergoing brief calorie restriction.
By using autophagy, dead or damaged cells can be removed and replaced with newer, more functional ones.
However, what about research involving actual people?
Health span, defined as the number of years someone lives in good health, may be affected by positive changes in risk factors of age-related diseases like cancer, diabetes, and cardiovascular disease.
Getting into ketosis may be easier if you take these seven steps.
A good way to ease into the Ketogenic diet is through an intermittent fasting protocol like the FMD.
It can aid the body in becoming fat-adapted while providing some of the potential benefits of fasting.
After that, you’ll be better prepared to switch to a high-fat, healthy diet. It’s easier on the body than suddenly switching to a Keto diet from the typical Western diet.
Potentially Protects Against Dangers Associated with Prolonged Water-Only Fasting
Pain, fatigue, insomnia, dehydration, and electrolyte imbalances are all possible side effects of supervised water-only fasting, but the treatment is generally considered fairly safe in certain situations.
It is hypothesised that you can achieve some of the benefits of water-only fasting with the 5-day FMD protocol, without the same level of risk and without necessarily having medical supervision, as you still consume a modest number of calories over the course of the fast.
Overall, the findings surrounding the FMD are encouraging, but further large-scale, long-term human studies are required before any firm conclusions can be drawn about the diet’s efficacy.
FMD’s Possible Drawbacks:
1. Cost
A ProLon kit subscription will set you back $240 per FMD cycle. Trying to do this on a regular basis (say, once every few months) can add up in price. We’ll dive deeper into the possibility of a do-it-yourself FMD diet in the following section.
2. Precautions to Take Note of
Before trying out the FMD on your own, make sure you have your doctor’s okay. As mentioned above, the protocol is not appropriate for women who are pregnant or breastfeeding, children, people with a history of eating disorders, and those with certain health conditions.
3. Complexity
Although the FMD is generally more manageable than water-only fasting, it still necessitates some preparation and determination to maintain. However, others report feeling completely normal during those five days, while still others report feeling exhausted. Taking into account how the diet will influence your schedule, ideally the protocol would be implemented during a week with few other commitments.
Are Keto FMDs possible? Attempting a fast-like diet at home.
It is possible to make your own Keto fasting meal replacement (FMD).
The good news is that you will likely have a slight advantage going into the FMD if you already follow a Ketogenic diet. Since you’re already fat-adapted, you may find that burning fat for fuel during the early stages of the fast is simpler.
Like the classic FMD, you want to limit protein while cutting back on carbohydrates and increasing fat.
Keto-friendly foods, such as: You could follow a similar format to tmerely exchanging the nut bars and soups for Keto-friendly foods, such as:
Soup made with bones
Nuts, seeds, and other seed products in their whole forms
Spreads made from nuts
Avocado
Coconut
In spite of the deviation from the standard protocol reflected in the macros, you should still strive to maintain a similar caloric intake (1090 kcal on Day 1, 725 kcal on Days 2-5).
Conclusion
There is some encouraging work being done on FMD in a variety of settings.
While more research is necessary, preliminary findings suggest it may aid weight loss efforts and promote general health.
It can be adapted to go well with the Keto diet. If you want to give it a try, see your doctor first.
References
1. Chen, Q., Polireddy, K., Chen, P., Balusu, R., Wang, T., & Dong, R. (2020). Pharmacologic Ascorbate Influences Multiple Cellular Pathways Preferentially in Cancer Cells. In Cancer and Vitamin C (pp. 33-44). CRC Press.
Link: https://www.taylorfrancis.com/chapters/edit/10.1201/9781003017493-3/pharmacologic-ascorbate-influences-multiple-cellular-pathways-preferentially-cancer-cells-qi-chen-kishore-polireddy-ping-chen-ramesh-balusu-tao-wang-ruochen-dong
2. ClinicalTrials.gov Identifier: NCT03146962. High Dose Vitamin C Intravenous Infusion in Patients with Resectable or Metastatic Solid Tumor Malignancies.
Link: https://link.springer.com/article/10.1007/s00277-015-2464-2
3. Mastrangelo D, Massai L, Lo Coco F, Noguera NI, Borgia L, Fioritoni G, et al. Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines. Ann Hematol. 2015;94(11):1807–16.
Link: https://clinicaltrials.gov/ct2/show/NCT03146962?term=NCT03146962&draw=2&rank=1
4. Vollbracht, C., Schneider, B., Leendert, V., Weiss, G., Auerbach, L., & Beuth, J. (2011). Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicenter, epidemiological cohort study in Germany. in vivo, 25(6), 983-990.
Link: https://iv.iiarjournals.org/content/25/6/983.short
5. Mansoor, F., Kumar, S., Rai, P., Anees, F., Kaur, N., Devi, A., … & Khan, S. (2021). Impact of intravenous vitamin C Administration in Reducing Severity of symptoms in breast Cancer patients during treatment. Cureus, 13(5).
Link: https://www.cureus.com/articles/58349-impact-of-intravenous-vitamin-c-administration-in-reducing-severity-of-symptoms-in-breast-cancer-patients-during-treatment
6. Kawada, H., Sawanobori, M., Tsuma-Kaneko, M., Wasada, I., Miyamoto, M., Murayama, H., … & Ando, K. (2014). Phase I clinical trial of intravenous L-ascorbic acid following salvage chemotherapy for relapsed B-cell non-Hodgkin’s lymphoma. Tokai J. Exp. Clin. Med, 39(3), 111-115.
Link: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://jeffreydachmd.com/wp-content/uploads/2017/06/Intravenous-Ascorbic-Acid-Following-Chemotherapy-for-Relapsed-B-Cell-Lymphoma-KAWADA-Hiroshi-Tokai-journal-2014.pdf
7. ClinicalTrials.gov Identifier: NCT04516681. IV Ascorbic Acid in Peritoneal Metastatic Colorectal Cancer.
Link: https://clinicaltrials.gov/ct2/show/NCT04516681?term=NCT04516681&draw=2&rank=1
8. Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., … & Levine, M. (2008). Pharmacologic doses of ascorbate function as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National Academy of Sciences, 105(32), 11105-11109.
Link: sciencedirect.com/science/article/pii/S2090123220300539
9. Qazilbash, M. H., Davis, M. S., Ana, A., Roden, L., Libunao, F., Thall, P. F., … & Giralt, S. A. (2005). Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan: A New Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
Link: https://ashpublications.org/blood/article/106/11/1159/117089/Arsenic-Trioxide-with-Ascorbic-Acid-and-High-Dose
10. Welch JS, Klco JM, Gao F, Procknow E, Uy GL, Stockerl-Goldstein KE, Abboud CN, Westervelt P, DiPersio JF, Hassan A, Cashen AF, Vij R. Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study. Am J Hematol. 2011 Sep;86(9):796-800. do: 10.1002/ajh.22092. Epic 2011 Aug 3. PMID: 21815182.
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