Top 10 Repurposed Drugs and Metabolic Interventions for Cancer Treatment: Evidence Based (2024)
This is a review of the published literature showing options for natural
strategies and repurposed drugs that can be used in cancer prevention and
treatment. It is not intended as a stand-alone guide to treating cancer. Nothing
in this document should be taken as a basis to initiate treatment without
guidance or avoid any treatment prescribed by your treating physician. This
information is offered as a basis to assist mutual decision-making. Cancer care
should always be supervised by a healthcare provider. Patients with cancer
should ALWAYS consult with their regular oncologist as well as an integrative
provider/oncologist, in addition to their primary care provider.
Related: Cancer Metabolism as a Therapeutic Target and Review of Interventions (Nutrients 2023)
Methodology
Related: Top 10 Cancer Fighting Supplements
Many of us were first exposed to the idea of using prescription drug
cocktails to treat cancer by Ben Williams. Mr. Williams was diagnosed with
glioblastoma in March 1995. He availed himself of a drug and supplement
protocol that proved to be effective. He chronicled these treatment choices
first on a
website and in his 2002 book,
Surviving Terminal Cancer: Clinical Trials, Drug Cocktails, and Other
Treatments Your Oncologist Won’t Tell You About. The protocol he followed stood out not just because of the many
nutritional supplements but also because he took multiple off-label drugs.
Williams took a range of drugs including Accutane, Actos, and Celebrex
that evidence suggested might have an additive or synergistic effect against
glioblastoma.
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| Chemotherapy has survival advantage on 'chemotherapy curable cancers' (left column) but chemotherapy does not have survival benefit for most cancers on the right column: FLCCC Alliance |
For evidence, we include first meta-analyses of clinical trials. If these are not available, we then include individual clinical trials. If these are not available, we include case series, and then case studies. If human studies are not available, we rely on preclinical evidence.
The saturated fat-cholesterol hoax
The Cholesterol-Saturated fatty acid hoax began to proliferate in the 1960s. Dr. Ancel Keys popularized the notion that saturated fats and high cholesterol were the primary causes of atherosclerotic heart disease — the so-called Diet-Heart Hypothesis. This concept has been vigorously studied, including in many randomized controlled trials, and has been convincingly proven to be false (BMJ 2016). Indeed, replacing saturated fats with a diet high in vegetable oils (linoleic acid) was associated with higher rates of death, cardiovascular and coronary heart disease as well as a significantly increased risk of cancer (BMJ 2013).
Avoid seed oils high in linoleic acid. Linoleic acid is an Omega-6 fatty
acid that our bodies require in small amounts. Unfortunately, many people
eat up to 10 times the desired amount of linoleic acid, because of excess
consumption of foods made with seed oils. Too much linoleic acid is
associated with inflammation, obesity, heart disease, and other unfavorable
conditions. Therefore, avoid:
A 2023 systematic review and meta-analysis of 14 RCTs
(randomized controlled trials), published in Ageing Research
Reviews (Kuznia 2023) found vitamin D3 supplementation reduced cancer mortality
by 6%. This wasn’t considered statistically significant, but
when only studies involving daily vitamin D intake were
analyzed, cancer mortality dropped by a significant 12%.
A Secondary Analysis of the VITAL Randomized Clinical Trial
studied the effect of Vitamin D3 Supplements on Development
of Advanced Cancer. The Harvard research, published in the
JAMA Network Open medical journal
(2020), overturns the initial findings of a study of 25,000
people published in 2018.
Initially researchers believed there was no benefit from taking vitamin D, as they detected no reduced incidence of cancer diagnoses overall. But they were puzzled because cancer deaths went down among those taking the supplements. Meaning, there was no benefit in terms of prevention of cancer but a reduction in cancer deaths was observed.
A secondary analysis, found this anomaly can be explained by the fact that vitamin D seems to stop metastatic cancers - those aggressive types which spread to other parts of the body. That said, when stratified by BMI (body mass index), there was no significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with overweight or obesity (BMI 25-<30).
The cancers for which the most human data are available are colorectal, breast, prostate, and pancreatic cancer. Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer (R). In contrast, the Women’s Health Initiative randomized trial found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer (NEJM 2006). Some scientists have pointed out that the relatively low level of vitamin D supplementation (10 μg, or 400 IU, once a day), the ability of participants to take additional vitamin D on their own, and the short duration of participant follow-up in this trial might explain why no reduction in colorectal cancer risk was found.
Multiple studies indicate that a significant proportion of cancer patients are vitamin D-deficient (level < 20 ng/mL) and that higher plasma 25-hydroxyvitamin D levels are associated with improved survival in colorectal, breast, gastric, and lymphoma cancer patients [Systematic Review 2014]. Meta-analyses and clinical trials demonstrate that vitamin D supplementation may reduce cancer mortality and improve survival in cancer patients, especially when used in combination with chemotherapy (Meta-analysis 2023). SUNSHINE (JAMA 2019), a clinical trial on metastatic colorectal cancer patients, showed that “high-dose” vitamin D3 (aiming for a level of >50 ng/mL) combined with standard chemotherapy resulted in improved progression-free survival compared to standard-dose vitamin D3.
Significantly, the active elements in curcumin attack cancer
while leaving healthy cells untouched. For the purpose of
disease intervention, while turmeric is available in powdered
form, it contains very little of the active compounds in
curcumin, or only about a 3% curcumin concentration.
Turmeric and black pepper each have health benefits, due to the compounds curcumin and piperine. As piperine enhances curcumin absorption in the body by up to 2,000%, combining the spices magnifies their effects. (Healthline)
*Umbrella review: An umbrella review, or a review of reviews, is a systematic review that only considers other systematic reviews as an eligible study type for inclusion.
2022 - A meta-analysis to review the association between vitamins and brain cancer
showed that intake of vitamin C, β-carotene, and folate can
reduce the risk of brain cancer, while high serum α-tocopherol
(vitamin E) concentration also has a protective effect on
brain cancer.
2022 - A systematic review on the effect of vitamins C and E on cancer survival
showed improvement of survival and progression rates of
cancers by vitamins C and E. However, the authors concluded
that more high quality trials with large sample sizes are
required to confirm.
High-dose vitamin C cancer therapy was introduced by Linus
Pauling and Ewan Cameron [R]. Clinical demonstration results by Pauling and Cameron
showed that intravenous injection of 10 g/day of vitamin C
extended the survival time of terminal cancer patients by
about 4.2 times. However, results from the Mayo Clinic in 1979
showed that the survival time of vitamin C–treated patients
was even shorter than that of the placebo group patients [R]. A significant difference between those two research groups
was the route of AA administration: intravenous injection and
oral administration, respectively.
Read More: Fenbendazole Cancer Success Stories and Treatment Testimonials: Case Series
Note: Most Molecular Hydrogen tablets uses pure elemental magnesium as its carrier and provides you with approximately 80 mg of magnesium per tablet. So, you receive also highly bioavailable magnesium for a healthy brain, muscles, cells, kidneys, and heart.
Numerous trials have shown that metformin, routinely used to treat diabetes, also inhibits the development of cancer cells and reduces cancer cell proliferation. Unlike most standard chemotherapy, metformin suppresses cancer stem cells, the root of cancer. (Shi 2017)
Many cancer patients also have type-2 diabetes. Yet few take
metformin because treating diabetes has taken a backseat to treating
their cancer. We check hemoglobin A1c status on all our cancer
patients. The medical standard of care is to prescribe metformin for
anyone with a 5.8% or higher A1c.
The results of the Taiwan National Health Insurance Data Survey (2019), which included a community of 12,005 patients taking
metformin from 2000 to 2007 and a population of 4,597 patients
taking other oral medications, indicated that using metformin
reduces the chance of any type of cancer up to 88%.
Meta-analyses have examined the role of metformin in the primary prevention of cancer, where it was found to significantly reduce overall cancer incidence (Gandini 2014). Lega et al (2014) performed a meta-analysis of 21 observational studies, evaluating the outcomes of diabetic patients with cancer who were receiving metformin. In this study, metformin was associated with a reduction in all-cause mortality and cancer-specific mortality; patients with colorectal cancer demonstrated the greatest benefit.
What are the Best Cancer Fighting Foods
Top 10 Alternatives and Metabolic Interventions to Control Cancer
The
Repurposing Drugs in Oncology (ReDO) project
has cataloged 268 approved drugs with anticancer effects. It would be
impossible to review all the drugs in ReDo’s database in this article;
rather, we have focused on, curated and evaluated the drugs or natural
compounds that appear to have the greatest clinical utility. These
repurposed drugs are listed in priority according to the strength of the
supporting clinical and mechanistic evidence.
SUMMARY OF TOP METABOLIC INTERVENTIONS TO CONTROL CANCER
List based on the quality of evidence.
- Low-carbohydrate Diet, keto diet, Intermittent Fasting and Cancer
- Vitamin D3, Omega 3 and Cancer
- Turmeric (Curcumin)
- Fenbendazole / Mebendazole / Albendazole and Cancer
- Vitamin C and E
- Molecular Hydrogen and Magnesium
- Metformin
- Ivermectin and Cancer
- Melatonin
- Mistletoe
1. Low-carbohydrate Diet, Keto Diet, Intermittent Fasting and Cancer
A carbohydrate-restricted diet (less than 25 g of carbs per day) that is high in saturated fat and Omega-3 fatty acids (ketogenic diet) is suggested. Avoid all processed food (see the FLCCC Guide to Fasting and Healthy Eating for more detailed guidance). Contrary to current dogma, saturated fatty acids are “healthy,” but you should avoid processed Omega-6 vegetable oils (see below). Avoid foods that are high on the glycemic index and follow the “hacks” to flatten the blood glucose curve (see below).
The saturated fat-cholesterol hoax
The Cholesterol-Saturated fatty acid hoax began to proliferate in the 1960s. Dr. Ancel Keys popularized the notion that saturated fats and high cholesterol were the primary causes of atherosclerotic heart disease — the so-called Diet-Heart Hypothesis. This concept has been vigorously studied, including in many randomized controlled trials, and has been convincingly proven to be false (BMJ 2016). Indeed, replacing saturated fats with a diet high in vegetable oils (linoleic acid) was associated with higher rates of death, cardiovascular and coronary heart disease as well as a significantly increased risk of cancer (BMJ 2013).
Healthy and unhealthy oils
• Soybean oil
• Corn oil
• Cottonseed oil
• Sunflower oil
• Sesame oil
• Grapeseed oil
• Safflower oil
• Margarine
• Rice bran oil
Instead, opt for healthy oils and fats such as the ones listed below. Use
only high-quality products and check production and expiration
dates.
• Olive oil (oleic acid, Omega-9 monounsaturated fatty acids); never heat
olive oil to the point where it produces smoke.
• Avocado oil (oleic acid, Omega-9 monounsaturated fatty acids)
• Coconut oil (medium chain fatty acid)
• Flaxseed oil (alpha-linolenic acid, ALA Omega-3)
• Walnut and Pecan oils; should be refrigerated to avoid spoilage
• Butter (saturated fat)
Low-Carb and Fasting Are Ill-Advised
As noted by Dr Peter Attia, weeklong fasting significantly deteriorates
thyroid function, and that can be explained by the lack of nutrients
during a fast. While he does not address this, the same applies to
low-carb eating and time-restricted eating (TRE). All three of these
strategies will activate your adrenals, trigger cortisol release and
down-regulate your thyroid function and metabolism.
So, while low-carb and various fasting regimens can be helpful in the
short term to address extreme obesity, there are safer,
albeit slower, ways to address that. As explained in "Important Information About Low Carb, Cortisol and Glucose", elevated cortisol is highly problematic, as it breaks down your lean
muscle, bones and brain to make amino acids that your liver then
converts to glucose. It also promotes inflammation and is a primary
driver of aging.
If cortisol is chronically elevated, you will likely die prematurely, as
it is highly catabolic, meaning it will break down your body tissues.
Cortisol is released when your body doesn’t have enough glucose
available, so it’s important to eat enough healthy carbs and not deprive
your body of glucose for extended periods.
Cautions and Concerns: Things to Consider Before Fasting
Fasting can have certain side effects, including mood swings and,
notably, hunger. In today’s culture, where snacking and constant
indulgence in food are common, fasting can be seen as equivalent to
starvation.
Dr. Jason Fung, a nephrologist and fasting expert, however, would argue that fasting is a purposeful way of managing one’s day by allocating specific times for eating.
The benefits of fasting can vary among individuals, and the preferred type of fasting can also differ. Intermittent fasting is generally safe, but not everyone responds well to prolonged fasting.
During prolonged fasts, the body primarily breaks down fat for energy rather than muscle. However, the extent to which fat or muscle is targeted can vary based on an individual’s body composition. Those who have more fat to lose may lose more fat and less muscle, while those with higher muscle mass may experience a greater breakdown of protein stores.
Studies have shown that lean muscle mass loss occurs within the first day of prolonged fasting, regardless of an individual’s fat and muscle proportions. Therefore, individuals with significant muscle mass may experience more muscle loss and less fat loss during prolonged fasting.
There are different approaches to incorporating fasting into one’s lifestyle, such as intermittent fasting or longer fasting periods every few months. Social norms, like having dinner together, can discourage extended fasting, so it’s important to choose a fasting style that suits one’s lifestyle and preferences.
However it should be noted that intermittent fasting is not recommended for:
Dr. Jason Fung, a nephrologist and fasting expert, however, would argue that fasting is a purposeful way of managing one’s day by allocating specific times for eating.
The benefits of fasting can vary among individuals, and the preferred type of fasting can also differ. Intermittent fasting is generally safe, but not everyone responds well to prolonged fasting.
During prolonged fasts, the body primarily breaks down fat for energy rather than muscle. However, the extent to which fat or muscle is targeted can vary based on an individual’s body composition. Those who have more fat to lose may lose more fat and less muscle, while those with higher muscle mass may experience a greater breakdown of protein stores.
Studies have shown that lean muscle mass loss occurs within the first day of prolonged fasting, regardless of an individual’s fat and muscle proportions. Therefore, individuals with significant muscle mass may experience more muscle loss and less fat loss during prolonged fasting.
There are different approaches to incorporating fasting into one’s lifestyle, such as intermittent fasting or longer fasting periods every few months. Social norms, like having dinner together, can discourage extended fasting, so it’s important to choose a fasting style that suits one’s lifestyle and preferences.
However it should be noted that intermittent fasting is not recommended for:
- People younger than the age of 18, as it can prevent growth.
- Pregnant and breastfeeding women are also not recommended to fast intermittently.
- Older people are notorious for getting frail very quickly if they skip even one meal. They don’t eat very often, but they need their meal. If you don’t give it to them, they can very quickly decline.
- Extended fasting is also not a healthy long term strategy as it increases your stress hormones and worsens mitochondrial function.
- People with diabetes and kidney disease are also recommended to check with their primary care physicians before considering intermittent fasting.
- Those taking hypoglycemic or antihypertensive medication are particularly at risk, as they may end up overdosing. If you're on medication, you need to work with your doctor to ensure safety, as some medications need to be taken with food and/or can become toxic when your body chemistry normalizes.
 |
| Credit: FLCCC 2024 Conference |
2. Vitamin D3, Omega 3 and Cancer
Vitamin D can absorb calcium and help the immune, muscle,
and nervous systems function properly. There are more than 11,000 search results on vitamin D and cancer on PubMed.
The first randomized-controlled trial (DO-HEALTH) trial to
investigate the combination of three complementary
treatments for the prevention of cancer and suggest that
the combination of daily vitamin D3, supplemental marine
omega-3s, and a simple home exercise program may be
effective in the prevention of invasive cancer among
generally healthy and active adults aged 70 and older.
Findings from a 3 year Randomized Controlled Trial with
more than 2,000 participants observed a 61% reduction in
the risk of invasive cancer among patients who completed
a
home exercise program and took vitamin D3 and omega-3 fatty acids daily.
These results, from the DO-HEALTH trial
(ClinicalTrials.gov identifier NCT01745263), were published in Frontiers in Aging 2022.
Initially researchers believed there was no benefit from taking vitamin D, as they detected no reduced incidence of cancer diagnoses overall. But they were puzzled because cancer deaths went down among those taking the supplements. Meaning, there was no benefit in terms of prevention of cancer but a reduction in cancer deaths was observed.
A secondary analysis, found this anomaly can be explained by the fact that vitamin D seems to stop metastatic cancers - those aggressive types which spread to other parts of the body. That said, when stratified by BMI (body mass index), there was no significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with overweight or obesity (BMI 25-<30).
The cancers for which the most human data are available are colorectal, breast, prostate, and pancreatic cancer. Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer (R). In contrast, the Women’s Health Initiative randomized trial found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer (NEJM 2006). Some scientists have pointed out that the relatively low level of vitamin D supplementation (10 μg, or 400 IU, once a day), the ability of participants to take additional vitamin D on their own, and the short duration of participant follow-up in this trial might explain why no reduction in colorectal cancer risk was found.
According to BreastCancer.org, research suggests that certain cancers such as breast cancer,
can have a higher risk of occurring when the
body has low levels of vitamin D.
Studies also show a link between vitamin D
deficiency and cardiovascular disease, diabetes,
and cancer (Sizar, 2020).
In 2016, a landmark study published in PLOS ONE found that women
over 55 with blood concentrations of vitamin D
higher than 40 ng/ml, had a 67% lower risk of
cancer compared women with levels lower than 20
ng/ml.
Many experts now recommend 800 to 1,000 IU a
day, a goal that's nearly impossible to attain
without taking a supplement. Although
protection is far from proven, evidence
suggests that vitamin D may help reduce the
risk of prostate cancer, colon cancer, and
other malignancies.
Types of cancers that Vitamin D may be
beneficial for
Vitamin D supplementation is likely
beneficial in most cancers, but particularly
in patients with breast, colorectal, gastric,
esophagus, lung, and prostate cancer as well
as those with lymphomas and
melanoma.
Although the role of vitamin D in cancer
prevention remains an area of research
interest and debate, avoiding deficient levels
is recommended. (American Cancer Society 2020)
Vitamin D can also be absorbed through sunlight,
or with the following diet:
- fatty fish
- egg yolks
- fortified milk
Make sure to take 500 mg to 1000 mg of magnesium and 150
mcg of vitamin K2, (not K1) which are important cofactors
for optimizing vitamin D function. And, remember the only
way you know what your vitamin D level is, is to test it.
Vitamin D level should be in a therapeutic range of 50 to
70 ng/ml for treatment of rheumatoid arthritis. Most
people are shocked how low their level is when they
finally get around to testing it.
Vitamin D and Chemotherapy
3. Turmeric (Curcumin) and Cancer
There are more than 7,000 search results on curcumin and cancer on PubMed and more than 50 clinical trials with curcumin, most of which are still ongoing. The
spice turmeric can be extremely helpful when it comes to
fighting cancer.
Studies show that the curcumin in turmeric may kill cancer cells and
slow tumor growth. This preclinical research has taken
curcumin from the lab to the clinic.
The benefits of curcumin may include:
- blocking cancer cells from multiplying
- killing colon, breast, prostate, and melanoma cancer cells
- slowing tumor growth
Most of the studies published on PubMed are non-human
(pre-clinical) studies.
A review paper published in 2022, analysed 21 human studies.
Sixteen out of 21 clinical trials were associated with
the effectiveness of curcumin or turmeric on various
types of cancer, and the other five clinical trials were
related to the evaluation of the efficacy of curcumin or
turmeric in relieving the side effects of cancer
chemotherapy and radiotherapy. The emerging data from
the clinical trials confirm that curcumin has the
potential for cancer prevention and intervention.
Because it's not easily absorbed through your
gastrointestinal tract, it's more effective to use a
high-quality bioavailable curcumin extract, according to
a 2013 study. A typical anticancer dose is just under 1 teaspoon of
curcumin extract three or four times daily.
Both curcuminoids and related turmeric products have been
sanctioned by the U.S. Food and Drug Administration (FDA)
as safe.
Turmeric and black pepper each have health benefits, due to the compounds curcumin and piperine. As piperine enhances curcumin absorption in the body by up to 2,000%, combining the spices magnifies their effects. (Healthline)
The use of fenbendazole and curcumin, has achieved much attention due to the reported experience of Joe Tippens. In 2016, Tippens was diagnosed with non-small-cell lung cancer with extensive metastatic disease. At the advice of a veterinarian friend, he took Fenbendazole together with nanocurcumin, and three months after starting these drugs his PET scan was completely clear. He remains alive and disease-free up until the present.
4. Vitamin C and E
PubMed has indexed more than 3,000 research studies on vitamin C and cancer and more than 5,000 studies on vitamin E and cancer.
Prevention
2022 - An umbrella review* (Xu 2022) to assess the existing systematic reviews and
meta-analyses for the association between vitamin C intake and
multiple health outcomes; showed that vitamin C intake was
associated with reduced risk of all-cause mortality,
cardiovascular disease (CVD), oesophageal cancer, gastric
cancer, cervical cancer and lung cancer with an increment of
50–100 mg per day.
Beneficial associations were also identified for respiratory,
neurological, ophthalmologic, musculoskeletal, renal and
dental outcomes. A total of 76 meta-analyses (51 papers) of
randomised controlled trials and observational studies with 63
unique health outcomes were identified. Harmful associations
were found for breast cancer and kidney stones for vitamin C
supplement intake.
*Umbrella review: An umbrella review, or a review of reviews, is a systematic review that only considers other systematic reviews as an eligible study type for inclusion.
2022 - Obese women who took vitamin C and B6 at amounts that
exceeded the recommended daily intake levels were associated
with a lower risk of breast cancer, according to a five-year
long South Korean cohort study. 40,432 women without a history of cancer at baseline were
included in this study.
Treatment
Vitamin C is known as an antioxidant, but at high
concentrations, vitamin C can kill cancer cells through a
pro-oxidant property (Transl Oncol. 2020). This study has also demonstrated that vitamin C
treatment with magnesium supplementation provided more
effective anticancer therapy than vitamin C treatment alone.
To understand the mechanism of AA's anticancer activity, many
research groups have treated colon, prostate, leukemia,
lymphoma, brain, and stomach cancer cells and chemically or
genetically transformed cancer cells with AA and showed cancer
growth inhibition and even cancer cell death through hydrogen
peroxide–mediated reactive oxygen species (ROS) generation [R]. In most cases, the pharmacological concentration of
vitamin C required for anticancer effects (EC50 value of 1–10
mM) could only be achieved by intravenous administration.
Thus, to apply vitamin C as an anticancer therapy, a high
intracellular concentration in cancer cells is critically
important (R).
5. Fenbendazole / Mebendazole / Albendazole and Cancer
The use of benzimidazoles in cancer is limited to a few case reports
and a small case series (Chiang 2021). Mebendazole (MBZ) is a component of the multidrug cocktail used
in the METRICS study (Agrawal 2019). The use of benzimidazoles, and in particular fenbendazole,
has achieved much attention as a repurposed drug for cancer due to
the reported experience of
Joe Tippens. In 2016, Tippens was diagnosed with non-small-cell lung cancer
with extensive metastatic disease. At the advice of a veterinarian
friend, he took Fenbendazole together with nanocurcumin, and three
months after starting these drugs his PET scan was completely clear.
He remains alive and disease-free up until the present.
Types of cancers that mebendazole may be beneficial for
A wide variety of cancers, including NSCLC (non small cell lung
cancer), adrenocortical, colorectal, chemo-resistant melanoma,
glioblastoma multiforme, colon, leukemia, osteosarcoma/soft tissue
sarcoma, acute myeloid sarcoma, breast (ER+ invasive ductal),
kidney, and ovarian carcinoma, have been shown to be responsive to
benzimidazoles, including MBZ. (Guerini 2019,
Meco 2023)
Dosing and cautions
We suggest Mebendazole 100-200 mg/day. The cost of mebendazole in
the U.S. skyrocketed once this drug was discovered to have activity
against cancer ($555 for a single 100 mg tablet). However,
mebendazole is available from international compounding pharmacies
(India) at about 27c for a 100 mg tablet.
6. Molecular Hydrogen and Cancer
In terms of cancer management or treatment, studies involving the effects of H2 on cancer were systematically reviewed. More than 600 articles related to molecular hydrogen and cancer were retrieved from Cochrane, PubMed and Google Scholar, and 27 articles were included for this systematic review (2023).
Based on the authors' analysis, "H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction."
Although H2 has demonstrated significant anti-cancer effects, the underlying mechanisms have not yet been elucidated. Many studies have shown that H2 therapy can reduce oxidative stress. This, however, contradicts radiation therapy and chemotherapy, in which ROS (Reactive Oxygen Species) are required to induce apoptosis and combat cancer.
Related: Best Molecular Hydrogen Tablets
7. Metformin
A search on PubMed for “metformin AND cancer” yielded more than 6,000 citations.Numerous trials have shown that metformin, routinely used to treat diabetes, also inhibits the development of cancer cells and reduces cancer cell proliferation. Unlike most standard chemotherapy, metformin suppresses cancer stem cells, the root of cancer. (Shi 2017)
Clinical studies
Meta-analyses have examined the role of metformin in the primary prevention of cancer, where it was found to significantly reduce overall cancer incidence (Gandini 2014). Lega et al (2014) performed a meta-analysis of 21 observational studies, evaluating the outcomes of diabetic patients with cancer who were receiving metformin. In this study, metformin was associated with a reduction in all-cause mortality and cancer-specific mortality; patients with colorectal cancer demonstrated the greatest benefit.
In a similar analysis performed by Yin et al (2013), metformin improved overall survival in patients
with lung, breast, and prostate cancer.
Coyle et al (2016) performed a meta-analysis of 27 observational
studies which investigated the use of metformin as an adjunctive
treatment for cancer. The findings of this study suggested that
metformin was associated with significant benefit in the early
treatment of patients with colorectal and prostate cancer,
particularly in those receiving radical radiotherapy.
Types of cancers that metformin may be beneficial for
Various malignancies can be prevented with the use of metformin.
In general, metformin can: i) lower cancer incidence, ii) lower
cancer mortality, iii) improve cancer cell response to
radiotherapy and chemotherapy, iv) optimize tumor migration and
lower malignancy, v) lower relapse risk, and vi) lessen the
harmful effects of androgen derivatives. (Saraei 2019)
Collective findings show that metformin has a broad spectrum of
anticancer activity against breast, pancreatic, gastric,
colorectal, endometrial, pancreatic prostate, non-small cell lung
cancer (NSCLC), and bladder cancers. (Buczyńska 2022, Stopsack 2016, Mei 2014) However, the greatest benefit may be in patients with
colorectal and prostate cancer, (Stopsack 2016, Mei 2014), particularly when used as an adjunctive therapy.
Dosing and cautions
A dose of metformin of 1,000 mg twice daily is suggested.
Metformin is a remarkably safe drug with very few side effects.
The most common adverse effects include abdominal or stomach
discomfort, cough, hoarseness, decreased appetite, and diarrhea.
Prolonged use is associated with vitamin B12 deficiency;
supplementation with a B complex vitamin is therefore suggested.
Metformin may cause very low blood glucose when combined with
berberine; hence the blood glucose should be very closely
monitored in patients taking this combination; if low glucose does
occur, we would suggest alternating metformin and berberine
(monthly).
8. Melatonin
PubMed has indexed more than 3,000 research studies on melatonin and cancer.
2022 - An umbrella review of meta-analyses based on randomized controlled trials (Pharmacological Research 2022):
"Survival at one year (P < 0.005) significantly increased with cancer patients."
Melatonin is one of the most important antioxidant molecules. In
the human body — aside from having direct antioxidant effects —
it also stimulates the synthesis of glutathione and other
important antioxidants like superoxide dismutase and catalase.
Many people are not aware that only 5% of your body’s melatonin
— which is also a potent anticancer agent — is produced in your
pineal gland. The other 95% is produced inside your mitochondria
— provided you get sufficient near infrared exposure which is
typically from sun on your bare skin. This is why vitamin D is
more than likely a biomarker for sun exposure, which is
intricately involved in melatonin production. (R)
Melatonin - Treatment
2020 - A case series of 14 advanced cancer patients (Trends in Oncology 2020), treated with high dose (1,000 mg/day) of melatonin;
achieved a disease control of 54% of the patients:
"Moreover, this preliminary study may also suggest that
high dose melatonin has no toxicity in cancer patients with
poor clinical status, as well as in healthy subjects."
9. Ivermectin and Cancer
In a 2021 review paper, the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death were discussed. Also reviewed was the prospects for the clinical application of ivermectin as an anticancer drug for cancer therapy.
In another study, published in Nature (2021), Ivermectin stimulates T-cells to invade and destroy tumors and synergizes with immune checkpoint blockade for treatment of breast cancer.
Clinical studies
While many in vitro studies have demonstrated the effectiveness of ivermectin against multiple cancers, the clinical effectiveness is limited to small case series. (De Castro 2020, Ishiguro 2022)
Dosing and cautions
The optimal dosing strategy with ivermectin is unclear. De Castro et al reported the use of 1mg/kg/day for up to 6 months in three pediatric patients with refractory AML without untoward side effects (De Castro 2020). Ishiguro et al reported the use of ivermectin 12 mg twice weekly. (Ishiguro 2022)
Read More: Ivermectin for Cancer: What You Need to Know
10. Mistletoe
Over 50 prospective studies (2020), including more than 30 randomized controlled trials (RCTs), have investigated the role of mistletoe in cancer patients, showing benefits in terms of improved quality of life, performance index, symptom scales, and reduced adverse effects of chemotherapy.Another 2022 review has further supported these findings, revealing that mistletoe extracts significantly improve global quality of life and may have a favorable effect on survival in cancer patients (HR = 0.81, 95% CI 0.69–0.95, p = 0.01) when used as in combination to conventional treatments.
A phase I trial (2023) of intravenous mistletoe extract in patients with advanced cancer showed a disease control rate of 23.8% and improved quality of life indicators. Mistletoe is commonly used by integrative oncologists to enhance quality of life, increase chemotherapy tolerability, and potentially contribute to better tumor control and survival.
Notes and Disclaimers:
- Please do not consider this guide as personal medical advice, but as a recommendation for use by professional providers. Consult with your doctor and discuss with her/him.
- Our aim here isn't to replace your doctors' advice. It is intended as a sharing of knowledge and information. Do take note that most treatments are not 100% protective or curative against cancer. It's a continuous struggle between the immune system and the cancer cells. Cancer treatments are meant to assist the immune system in this battle.
- Cancer treatment should be part of a multi-modal approach in order to provide the best possible outcome. Diet and lifestyle changes are also meant to run alongside conventional treatment. That said, there is no miracle treatment that can cure all cancers.
References:
- Repurposed Drugs for Cancer (Townsend Letter)
For more information on treatment, causes and prevention, screening, and the latest research, check out this comprehensive resource page (by cancer type) from National Cancer Institute: https://www.cancer.gov/types.
Related:
CAR-T vs CAR-NK - The Cancer Cell Therapy Showdown
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| 10 Alternative Cancer Therapies Worth Considering for an Integrative Treatment Plan (credit: briomedical) |
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