Redefining
Cancer
Treatment
Redefining
Cancer
Treatment
| Formulation | Typical Price Range (£) | Details/Notes |
|---|---|---|
| Tablets/Capsules (single) | £9 – £17 (60–100 caps) | Standard doses (5,000–10,000 IU per tablet/capsule)245 |
| Tablets (bulk, 1-year) | £14 – £16 (365 tabs) | 10,000 IU per tablet, 1-year supply2 |
| Beta-carotene tablets | £13 – £16 (100 tabs) | Vegan options available4 |
| Liquid drops (30–50ml) | £9 – £21 | Includes pure vitamin A and mixed ADEK formulas34 |
| Multivitamin drops (children) | £9 – £18 (50ml) | Contains vitamin A plus other vitamins3 |
| Vitamin A + D/E/K blends | £9 – £17 (60–100 caps/drops) | Fat-soluble blends |
Click 
Vitamin A, traditionally known for its role in vision and skin health, has garnered significant scientific interest for its potential anti-cancer properties. Research over recent decades has explored both the preventive and therapeutic roles of vitamin A and its derivatives (retinoids and carotenoids) in various cancers.
Vitamin A and its derivatives regulate cell proliferation, growth, and differentiation, processes that are often disrupted in cancer. Retinoids can induce growth arrest, promote apoptosis (programmed cell death), and encourage the re-differentiation of malignant cells, thereby inhibiting tumour progression145.
As a potent antioxidant, vitamin A helps neutralise free radicals, reducing oxidative stress and tissue damage that can lead to cancer initiation and progression13.
Both retinol (preformed vitamin A) and carotenoids (provitamin A) have demonstrated the ability to inhibit cell proliferation and increase apoptosis in cancer cell lines, particularly in breast cancer research1.
Multiple studies have highlighted an inverse relationship between serum levels of vitamin A or carotenoids and the risk of several cancers, including breast, cervical, skin, prostate, oral, and leukaemia134.
Clinical trials have shown that vitamin A supplementation can improve therapeutic responses in certain cancers. For example, oral vitamin A reduced chemoresistance in gestational trophoblastic neoplasia and enhanced the response to chemotherapy in advanced cervical carcinoma23.
Retinoic acid, a derivative of vitamin A, is an established treatment for acute promyelocytic leukaemia (APL), demonstrating the clinical utility of vitamin A compounds in oncology5.
| Cancer Type | Evidence for Benefit | Notes |
|---|---|---|
| Breast | Inverse association with risk | Lower serum levels in patients; conflicting evidence exists13 |
| Cervical | Improved response to chemotherapy | Supplementation shown to enhance treatment outcomes23 |
| Leukaemia (especially APL) | Established therapeutic use | Retinoic acid is a standard treatment5 |
| Skin, Prostate, Oral, GI | Inhibitory effects observed in vitro | Role in prostate cancer prevention remains unclear4 |
| Pancreatic, Bladder | Potential benefit in cell studies | Further research needed35 |
While many studies suggest a protective effect, some epidemiological data do not find a significant association between vitamin A or carotenoid intake and reduced cancer risk, particularly in prostate cancer134.
High-dose carotenoid supplementation has been associated with increased lung cancer risk in smokers, highlighting the need for caution and individualised recommendations1.
The mechanisms by which vitamin A exerts anti-cancer effects are complex and not entirely dependent on retinoic acid receptor pathways. Recent studies suggest that retinol itself may have unique anti-cancer actions not mediated by these receptors5.
Vitamin A is generally safe when consumed at recommended dietary levels, but excessive intake can be toxic.
Its use as an adjunct in cancer therapy is promising, especially in combination with conventional treatments, but requires further research to determine optimal dosing and patient selection2345.
Vitamin A and its derivatives show promising anti-cancer properties through multiple mechanisms, including antioxidant activity, regulation of cell growth, and induction of apoptosis. While there is substantial evidence supporting their preventive and therapeutic roles in certain cancers, the benefits can vary depending on cancer type, patient population, and form of vitamin A used. More research is needed to clarify optimal use, especially in clinical settings, and to identify patient groups most likely to benefit from vitamin A-based interventions12345.
A recommended safe dosage for vitamin A has been well established by health authorities:
Men: 700 micrograms (µg) per day
Women: 600 µg per day
You should not exceed a total intake of 1,500 µg (1.5 mg) per day from food and supplements combined1.
Vitamin A is fat-soluble and stored in the body, so excess intake over time can lead to toxicity.
The upper limit (UL) of 3,000 µg RAE per day applies to preformed vitamin A (retinol and retinyl esters) from both food and supplements2456789.
Beta-carotene and other provitamin A carotenoids from plant sources do not have the same toxicity risk, but high-dose supplements are not recommended, especially for smokers9.
Consistently exceeding the upper limit can cause serious side effects, including liver damage, bone thinning, and birth defects if taken during pregnancy3457.
The NHS specifically advises not to take more than 1.5 mg (1,500 µg) of vitamin A per day from all sources, particularly if you eat liver or liver products regularly1.
| Group | Recommended Daily Intake | Upper Safe Limit (UL) |
|---|---|---|
| Adult men | 700–900 µg RAE | 3,000 µg RAE (10,000 IU) |
| Adult women | 600–700 µg RAE | 3,000 µg RAE (10,000 IU) |
| Pregnant women | 770 µg RAE | 3,000 µg RAE (10,000 IU) |
| Children | Varies by age | Varies by age |
Vitamin A is safe and beneficial at recommended levels, but supplementation should not exceed 3,000 µg RAE (10,000 IU) per day for adults to avoid toxicity.
Most people can meet their needs through a balanced diet without supplementation.
Breast Cancer, Leukemia
Vitamin A can cause a range of side effects, particularly when taken in high or therapeutic doses, such as those sometimes used in cancer treatment.
Nausea and vomiting
Headache
Blurred vision
Drowsiness and irritability
Muscular weakness
Rash and skin peeling
Dryness of skin and mucous membranes
Abdominal pain
Elevated liver function tests and liver toxicity
Increased serum triglycerides
Asymptomatic hypercalcaemia (rarely)
Joint pain (arthralgia)
| Type of Toxicity | Typical Causes and Symptoms |
|---|---|
| Acute | Large, single dose (usually accidental, e.g. in children). Symptoms: headache, drowsiness, abdominal pain, nausea, vomiting, rash, irritability. Symptoms usually resolve after stopping intake45. |
| Chronic | Prolonged intake of high doses (10,000 IU/day or more in adults). Symptoms: changes in skin, hair, and nails, liver toxicity, increased intracranial pressure, bone pain, hypercalcaemia, risk of osteoporosis, and in pregnancy, birth defects145. |
Therapeutic doses for cancer are often much higher than standard dietary recommendations. In clinical trials, doses ranged from 100,000 IU/m² to 350,000 IU/m² per day. At these levels, the following toxicities have been reported:
Neuropsychiatric changes (e.g. mood alterations, confusion) were the earliest dose-limiting toxicities, occurring in patients receiving more than 240,000 IU/m² for 3–4 months.
Hepatomegaly (enlarged liver) and biopsy-proven liver toxicity developed in some patients at doses above 270,000 IU/m².
Elevated triglycerides were observed at 200,000 IU/m².
Skin and mucous membrane dryness was common above 150,000 IU/m².
Chronic liver toxicity and significant hepatotoxicity have occurred at doses as low as 20,000 IU, especially in those who consume alcohol regularly12.
For future cancer trials, a dose of 200,000 IU/m²/day was recommended due to toxicity concerns2.
Some studies suggest vitamin A supplementation may improve therapeutic response and reduce side effects in certain cancers, but others indicate no survival benefit or even increased risk of recurrence and death when used during chemotherapy3.
High-dose vitamin A (especially when combined with beta-carotene) has been linked to increased lung cancer risk and mortality in smokers345.
There is concern that antioxidants like vitamin A may counteract the intended effects of chemotherapy and radiotherapy by protecting both healthy and cancerous cells from oxidative damage3.
| Side Effect | Acute Toxicity | Chronic Toxicity | High-Dose Cancer Therapy |
|---|---|---|---|
| Headache | Yes | Yes | Yes |
| Nausea/Vomiting | Yes | Sometimes | Yes |
| Liver toxicity | Rare | Yes | Yes (dose-limiting) |
| Skin/mucous dryness | Sometimes | Yes | Yes (common at >150,000 IU/m²) |
| Neuropsychiatric changes | Rare | Yes | Yes (at >240,000 IU/m²) |
| Hypercalcaemia | Rare | Yes | Rare |
| Bone pain/osteoporosis | No | Yes | Possible |
| Birth defects (pregnancy) | No | Yes | Yes |
Vitamin A, particularly at therapeutic doses for cancer, can cause significant side effects, most notably liver toxicity, neuropsychiatric symptoms, and skin changes. Acute toxicity is rare but possible with large single doses, while chronic toxicity is a risk with prolonged high intake. Cancer patients considering vitamin A supplementation should do so only under strict medical supervision, as the risks can outweigh the benefits, especially at high doses or when combined with other treatments.
Vitamin A and its derivatives have been extensively tested in combination with other therapies for various cancers, both in clinical trials and preclinical studies.
Pancreatic Cancer:
The STARPAC phase I clinical trial in the UK demonstrated that adding all-trans retinoic acid (ATRA, a form of vitamin A) to standard chemotherapy for pancreatic cancer is safe, with no additional harmful effects compared to chemotherapy alone. This combination appears to modify the tumour stroma, potentially making the cancer more responsive to treatment. A follow-up phase II trial (STARPAC2) is underway to evaluate whether ATRA enhances the efficacy of chemotherapy in these patients12310.
Cervical Cancer:
A randomised double-blind clinical trial found that supplementing neoadjuvant chemotherapy (cisplatin and paclitaxel) with vitamin A (8,000 IU every 8 hours) improved tumour shrinkage in advanced cervical carcinoma compared to chemotherapy alone, though the difference did not reach statistical significance in the small sample. The results suggest vitamin A may enhance the response to chemotherapy in cervical cancer67.
Acute Promyelocytic Leukaemia (APL):
ATRA, in combination with arsenic trioxide, has become a standard, highly effective treatment for APL, allowing many children to avoid conventional chemotherapy altogether. Nearly all patients in a recent trial survived two years without relapse5.
Radiotherapy:
Preclinical studies have shown that combining ATRA with radiotherapy significantly improves tumour control compared to either treatment alone. This combination not only inhibited growth of irradiated tumours but also had an effect on distant, non-irradiated tumours, suggesting an immune-mediated benefit9.
Other Chemotherapy Agents:
Laboratory research has demonstrated synergistic effects when all-trans retinoic acid is combined with paclitaxel (a chemotherapy drug), resulting in greater tumour cell death than with either agent alone7.
Vitamin A analogues have also been tested as neoadjuvant agents with doxorubicin and methotrexate, showing potential to improve chemotherapeutic outcomes812.
Gestational Trophoblastic Neoplasia:
Oral vitamin A (6,000 IU/day) given with methotrexate chemotherapy reduced chemoresistance and tumour marker levels in patients with low-risk gestational trophoblastic neoplasia7.
Cautions and Contradictory Findings:
Not all combinations have been beneficial. For example, a study found that combining beta-carotene and vitamin A had no benefit and may have increased lung cancer incidence and mortality in smokers11.
| Cancer Type | Combination Therapy | Outcome/Effectiveness | Safety |
|---|---|---|---|
| Pancreatic cancer | ATRA + chemotherapy | Safe, modifies tumour stroma, phase II ongoing | No additional harm observed |
| Cervical cancer | Vitamin A + neoadjuvant chemotherapy | Improved tumour shrinkage | No significant added toxicity |
| Acute promyelocytic leukaemia | ATRA + arsenic trioxide | Highly effective, avoids chemotherapy | Well-tolerated |
| Solid tumours (preclinical) | ATRA + radiotherapy | Enhanced tumour control, immune effect | Noted in animal models |
| Gestational trophoblastic neoplasia | Vitamin A + methotrexate | Reduced chemoresistance | No major safety issues |
| Lung cancer (smokers) | Beta-carotene + vitamin A | Increased risk, not recommended | Potentially harmful |
Vitamin A and its derivatives have shown promise when combined with chemotherapy, radiotherapy, and targeted agents in several cancer types, with evidence of improved efficacy and safety in many settings. However, results can vary by cancer type, combination, and patient population, and some combinations (notably with beta-carotene in smokers) may be harmful. Ongoing clinical trials will further clarify its role in combination cancer therapy.
US National Library of Medicine research on Vitamin A
Europe PMC research on Vitamin A
Pubmed research on Vitamin A
Therapeutic levels of vitamin A, particularly in the form of retinoids, can have both positive and negative impacts on quality of life for individuals undergoing cancer treatment.
Improved Overall Health: Vitamin A supplementation has been associated with enhanced survival rates and reduced adverse effects during cancer treatment, contributing to better overall health24.
Symptom Reduction: In some studies, vitamin A has helped alleviate symptoms such as fatigue, nausea, and pain, which are common during chemotherapy2.
Enhanced Therapeutic Response: Vitamin A, especially when combined with other treatments like chemotherapy, can improve therapeutic outcomes in certain cancers, such as cervical carcinoma24.
Toxicity and Side Effects: High doses of vitamin A can lead to toxicity, causing symptoms like headaches, dizziness, and liver dysfunction. These side effects can significantly impact quality of life5.
Interference with Cancer Treatment: As an antioxidant, vitamin A may counteract the oxidative stress induced by chemotherapy and radiotherapy, potentially reducing their effectiveness. This could indirectly affect quality of life by prolonging treatment duration or reducing its efficacy24.
Increased Risk in Specific Populations: High doses of vitamin A, especially when combined with beta-carotene, have been linked to increased lung cancer mortality in smokers, highlighting a potential negative impact on quality of life for this group24.
Patient-Specific Outcomes: The impact on quality of life varies significantly among individuals, depending on cancer type, treatment regimen, and individual tolerance to vitamin A.
Monitoring and Dose Adjustment: Close monitoring by healthcare providers is crucial to balance therapeutic benefits with potential side effects, ensuring that vitamin A supplementation enhances rather than detracts from quality of life.
| Aspect of Quality of Life | Positive Effects | Negative Effects | Notes |
|---|---|---|---|
| Overall Health | Enhanced survival, reduced adverse effects | Potential toxicity | Therapeutic context |
| Symptom Management | Alleviates fatigue, nausea, pain | Side effects like headaches | Cancer treatment setting |
| Therapeutic Response | Improved outcomes in certain cancers | May interfere with chemotherapy efficacy | Specific cancer types |
| Safety and Toxicity | Generally safe at recommended doses | High doses can be toxic | Monitoring required |
Therapeutic levels of vitamin A can improve quality of life by enhancing overall health and reducing symptoms during cancer treatment. However, potential side effects and interactions with other therapies necessitate careful management to ensure these benefits are maximised while minimising negative impacts.
We’ve done our best to include as much information as possible for this supplement.
If you have any other questions, please send us a message or join our Skool Group and ask our knowledgeable and friendly community.
Vitamin A supplements are widely available over the counter in most countries. However, specific formulations used in cancer treatment, such as ATRA, may require a prescription and regulatory status may vary globally.
Current evidence suggests that the benefit of vitamin A for cancer prevention and therapy may vary by demographic factors, cancer type, and geographic region, but a single, universally defined patient demographic has not been conclusively established. However, several patterns have emerged from recent research:
High dietary intake or supplementation of vitamin A is associated with a reduced incidence of breast, ovarian, and cervical cancers in women, particularly in North American and Asian populations2.
The protective effect appears most significant for breast and ovarian cancers, with moderate increases in dietary vitamin A intake or supplements recommended for women at high risk of these cancers2.
The benefit is linked to dietary intake or supplementation, rather than high circulating vitamin A concentrations in the blood2.
The protective association of vitamin A intake is stronger in North America and Asia, and less pronounced in Europe and Oceania, possibly due to differences in diet, nutritional status, and genetic factors2.
Heterogeneity in results may also be influenced by ethnicity, socioeconomic status, and other region-specific factors2.
Most evidence for benefit is in breast, ovarian, and cervical cancers in women23.
There is less consistent evidence for benefit in prostate cancer, with some studies showing no significant correlation between vitamin A status and prostate cancer risk3.
Vitamin A and its derivatives are established as part of therapy for certain leukaemia’s (e.g., acute promyelocytic leukaemia), but this is based on disease biology rather than demographic factors3.
Late-stage breast cancer patients have been observed to have lower serum vitamin A levels, suggesting a potential role for supplementation in this group, though causality is not established4.
The impact of vitamin A may also be influenced by factors such as nutritional structure, economic development, HPV vaccination status (for cervical cancer), and other lifestyle variables2.
| Demographic/Group | Evidence of Benefit | Notes |
|---|---|---|
| Women (North America, Asia) | Strong | Breast, ovarian, cervical cancer prevention |
| Women (Europe, Oceania) | Weaker/less clear | Regional dietary and genetic differences |
| High-risk women (family history, etc) | Moderate | Especially for breast/ovarian cancer |
| Men (general population) | Inconclusive | No clear benefit for prostate cancer |
| Late-stage breast cancer patients | Observed low serum levels | Supplementation potential, not conclusive |
| Ethnic minorities (varies by region) | Possible | Data suggest regional/ethnic heterogeneity |
The groups most likely to benefit from vitamin A for cancer prevention are women in North America and Asia at risk for breast, ovarian, and cervical cancers, particularly through increased dietary intake or supplementation. There is insufficient evidence to define a precise demographic for therapeutic benefit in established cancer, beyond specific indications such as acute promyelocytic leukaemia. The effect in other populations and cancer types remains less clear and may be influenced by regional, ethnic, and lifestyle factors234.
Several genetic and molecular markers have been identified that influence resistance to vitamin A-based therapies in cancer. These markers impact metabolic pathways, receptor signalling, and tumour microenvironment interactions, modulating therapeutic outcomes.
ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)
Elevated in hepatic metastases and cancer stem cells (CSCs), ALDH1A1 promotes resistance by maintaining stem-like properties and detoxifying chemotherapeutic agents12.
In non-small cell lung cancer (NSCLC), ALDH1-positive CSCs resist cisplatin, but targeting the vitamin A/retinoic acid (RA) axis depletes these cells and restores chemosensitivity2.
CYP26B1 (Cytochrome P450 Family 26 Subfamily B Member 1)
RAR/RXR Receptor Dysregulation
Reduced expression of retinoic acid receptors (RARβ) or retinoid X receptors (RXR) in tumours disrupts RA-mediated gene regulation, leading to retinoid resistance9.
SCARB1 (Scavenger Receptor Class B Member 1)
RALDH (Retinaldehyde Dehydrogenase)
Overexpression in hepatic stellate cells (HSCs) increases RA synthesis, creating an immunosuppressive microenvironment that resists checkpoint blockade in liver metastases5.
| Marker/Pathway | Mechanism of Resistance | Cancer Relevance |
|---|---|---|
| ALDH1A1 | Sustains CSC populations and chemoresistance | NSCLC, colorectal, hepatic metastases |
| CYP26B1 | Accelerates RA degradation | Breast, prostate, neuroblastoma |
| RAR/RXR dysfunction | Disrupts RA-dependent gene regulation | Breast, leukaemia, skin cancers |
| SCARB1 variants | Reduces β-carotene uptake and retinol synthesis | General cancer prevention |
| Hepatic RA overproduction | Induces immune tolerance in liver metastases | Colorectal, pancreatic metastases |
Liver metastases show heightened resistance to immunotherapy due to high RA levels from vitamin A stored in HSCs5. Inhibiting RA synthesis (e.g., with disulfiram) may enhance checkpoint inhibitor efficacy5.
Ethnic variability in allele frequencies of SCARB1, BCMO1, and RBP4 affects vitamin A status and therapeutic response101316.
Retinoid resistance in solid tumours (e.g., breast, prostate) is linked to RARβ silencing or CYP26B1 overexpression, necessitating combination therapies39.
Resistance to vitamin A’s anti-cancer effects arises from genetic variants (ALDH1A1, CYP26B1, SCARB1), receptor dysregulation (RAR/RXR), and microenvironmental factors (hepatic RA overproduction). These markers highlight the need for personalised approaches, such as genetic testing to identify at-risk populations and combinatorial strategies to overcome resistance2516.
Pre-clinical studies have been pivotal in establishing the anti-cancer potential of vitamin A and its derivatives (retinoids), particularly in pancreatic, colorectal, neuroblastoma, and other cancers.
Key findings from these trials include:
Mechanism of Action:
In pancreatic cancer models, all-trans retinoic acid (ATRA) reversed the tumour-promoting behaviour of stellate cells, which form a protective stromal barrier around tumours. ATRA restored vitamin A levels in stellate cells, converting them into anti-cancer cells that reduced tumour proliferation and invasion158.
Combining ATRA with chemotherapy (e.g., gemcitabine) disrupted stromal-tumour communication, enhancing chemotherapy efficacy in preclinical models15.
Retinoid Activity:
Natural and synthetic retinoids demonstrated anti-proliferative, pro-apoptotic, and differentiation-inducing effects in CRC cell lines and animal models. These effects were mediated through retinoic acid receptor (RAR) pathways and modulation of Wnt/β-catenin signalling4.
Retinoids also inhibited metastasis by suppressing epithelial-mesenchymal transition (EMT) and angiogenesis4.
Differentiation Therapy:
ATRA induced differentiation of neuroblastoma cell lines into mature neuronal phenotypes in vitro. This led to reduced tumour aggressiveness and provided a rationale for clinical testing6.
Pharmacokinetic studies in Rhesus monkeys revealed ATRA’s short plasma half-life (45 minutes) and saturable elimination, prompting intermittent dosing strategies to maintain therapeutic efficacy6.
Retinol vs. Retinoic Acid:
Retinol (the most abundant circulatory form of vitamin A) exhibited anti-cancer effects in refractory cancers unresponsive to retinoic acid (RA), suggesting RA receptor-independent mechanisms3.
Synthetic retinoid derivatives (e.g., p-DDAP) showed selective toxicity against cancer cells with minimal side effects in mice3.
Liposomal and Nanoparticle Delivery:
| Cancer Type | Model System | Key Finding | Clinical Translation |
|---|---|---|---|
| Pancreatic | Mice, cell cultures | ATRA reprograms stroma, enhances chemotherapy | Phase I/II trials (STARPAC)15 |
| Colorectal | Cell lines, mice | Retinoids inhibit proliferation/metastasis | Limited clinical testing4 |
| Neuroblastoma | Cell lines, primates | ATRA induces differentiation | Paediatric phase II trials6 |
| Refractory cancers | Mice, cell cultures | Retinol and synthetic derivatives effective | Early-stage trials3 |
Pre-clinical trials have demonstrated vitamin A’s ability to modulate tumour microenvironments, induce differentiation/apoptosis, and synergise with chemotherapy. These findings underpinned clinical trials such as STARPAC for pancreatic cancer and neuroblastoma studies. Challenges remain in optimising retinoid formulations and overcoming resistance mechanisms, but pre-clinical data strongly support further investigation of vitamin A in oncology.
Vitamin A, particularly in the form of all-trans retinoic acid (ATRA), continues to be actively studied in a range of cancer clinical trials worldwide.
Below is a summary of current trials and their phases:
STARPAC2 Trial (UK):
This is a phase II randomised controlled trial evaluating ATRA in combination with standard chemotherapy (gemcitabine and nab-paclitaxel) for advanced pancreatic cancer. The phase I STARPAC trial established safety and tolerability; STARPAC2 is now investigating efficacy238.
NCT05999812 (USA):
This is a phase II, single-arm, open-label trial combining ATRA, bevacizumab, and atezolizumab for patients with refractory microsatellite stable metastatic colorectal cancer (MSS mCRC). The trial includes a safety lead-in phase and will assess response rates and adverse events101420.
APLUS Study (NCT04433169, China):
This ongoing phase II trial is investigating ATRA combined with low-dose apatinib in recurrent/metastatic adenoid cystic carcinoma of the head and neck. Preliminary results are promising, and the study is continuing to confirm efficacy and safety12.
Multiple Trials (Global):
Numerous ongoing studies are evaluating ATRA in haematological disorders, including:
Acute promyelocytic leukaemia (APL) (7 trials)
Non-APL acute myeloid leukaemia (AML) (4 trials)
Myelodysplastic syndromes (MDS) (3 trials)
Immune thrombocytopenia (ITP) (2 trials)
Autoimmune anaemia (1 trial)
Multiple myeloma (MM) (1 trial)
Many of these are combination therapy trials, with phases ranging from I to III61618.
NCI-2025-01522 (USA):
This trial is testing high-dose vitamin A supplementation to reduce the incidence of moderate to severe chronic graft-versus-host disease in allogeneic stem cell transplantation. The specific phase is not noted but is likely an early-phase (I/II) study1.
| Cancer/Condition | Vitamin A Formulation | Trial Phase | Combination/Focus | Reference |
|---|---|---|---|---|
| Pancreatic cancer | ATRA | II | With chemotherapy (STARPAC2) | 238 |
| Colorectal cancer (MSS mCRC) | ATRA | II | With bevacizumab and atezolizumab | 101420 |
| Head and neck cancer (R/M ACCHN) | ATRA | II | With low-dose apatinib (APLUS study) | 12 |
| Haematological cancers (APL, AML) | ATRA | I–III | Various combinations | 61618 |
| Stem cell transplantation | Vitamin A | I/II | High-dose supplementation | 1 |
Vitamin A (primarily as ATRA) is currently part of several active clinical trials, most notably phase II studies in pancreatic and colorectal cancers, as well as ongoing trials in head and neck and haematological cancers. These studies are exploring both efficacy and safety, often in combination with other therapies. Results from these trials will further clarify the therapeutic potential and optimal use of vitamin A in oncology.
Several genetic markers have been identified that affect vitamin A metabolism, bioavailability, and therapeutic efficacy, particularly in cancer contexts. These variations influence how individuals absorb, convert, and utilise vitamin A, impacting its effectiveness in prevention and treatment.
BCMO1 (Beta-Carotene Oxygenase 1)
RBP4 (Retinol-Binding Protein 4)
SCARB1 (Scavenger Receptor Class B Member 1)
CYP26B1
TTR (Transthyretin)
RAR/RXR (Retinoic Acid Receptor/Retinoid X Receptor)
Retinoid Resistance: Tumours with reduced RARβ expression or altered RAR/RXR signalling pathways may resist retinoid therapies416.
Ethnic Variability: Allele frequencies of SNPs (e.g., in BCMO1) differ across populations, contributing to disparities in vitamin A status and efficacy1215.
GWAS Insights: A 2024 study identified eight common, and one rare genetic variant linked to circulating retinol levels, highlighting roles in lipid metabolism and energy homeostasis. Mendelian randomisation suggested retinol influences inflammation and adiposity, which may modulate cancer risk15.
Personalised Supplementation: Genetic testing for variants (e.g., BCMO1, RBP4) can identify individuals prone to deficiency or poor retinoid response, enabling tailored diets or direct retinol supplementation612.
Therapeutic Targeting: In non-small cell lung cancer (NSCLC), ALDH1-positive cancer stem cells are depleted by retinoic acid axis modulation, suggesting genotype-specific treatment strategies47.
| Gene | Function | Impact of Variants | Cancer Relevance |
|---|---|---|---|
| BCMO1 | Beta-carotene → retinol conversion | Reduced retinol synthesis | Limits dietary efficacy in prevention |
| RBP4 | Retinol transport | Lower serum retinol, tissue deficiency | Affects therapeutic bioavailability |
| CYP26B1 | Retinoic acid degradation | Altered retinoic acid levels | Influences differentiation therapy |
| RAR/RXR | Gene regulation via retinoic acid | Impaired tumour suppression pathways | Linked to retinoid resistance in cancers |
These genetic insights underscore the need for personalised approaches to vitamin A supplementation and therapy, particularly in oncology, where efficacy depends on individual metabolic and genomic profiles.
Explore the fascinating world of molecular hydrogen (H₂) and its emerging role as a supportive treatment for cancer. Drawing on
Website designed in collaboration with Simon Lown for Metabolic Therapy Ltd
Apoptosis, or programmed cell death, is a natural process where cells self-destruct when they are damaged or no longer needed. This is crucial for maintaining healthy tissues and preventing diseases like cancer.
Drugs and supplements that induce apoptosis help eliminate cancerous cells by triggering this self-destruct mechanism, ensuring that harmful cells are removed without damaging surrounding healthy tissue.
Understanding and harnessing apoptosis is vital in the fight against cancer, as it targets the root cause of the disease at the cellular level.
Cell proliferation is the process by which cells grow and divide to produce more cells. While this is essential for growth and healing, uncontrolled cell proliferation can lead to cancer.
Drugs and supplements that inhibit cell proliferation help prevent the rapid multiplication of cancerous cells, slowing down or stopping the progression of the disease.
By targeting the mechanisms that drive cell division, these treatments play a vital role in controlling and potentially eradicating cancer.
Cancer cells often hijack specific biological pathways to grow and spread. Drugs and supplements that target these pathways can disrupt the cancer cell’s ability to survive and multiply.
By focusing on the unique mechanisms that cancer cells use, these treatments can be more effective and cause fewer side effects compared to traditional therapies.
Targeting specific pathways is a key strategy in precision medicine, offering a tailored approach to combat cancer at its core.
Angiogenesis is the process by which new blood vessels form, supplying nutrients and oxygen to tissues. Cancer cells exploit this process to fuel their growth and spread.
Drugs and supplements that inhibit angiogenesis can effectively starve cancer cells by blocking the formation of these new blood vessels.
By cutting off the supply lines that tumors rely on, angiogenesis inhibitors play a crucial role in controlling and potentially shrinking cancerous growths.
Immunotherapy harnesses the power of the body’s immune system to combat cancer. By boosting or restoring the immune system’s natural ability to detect and destroy cancer cells, immunotherapy offers a targeted and effective approach to treatment.
Drugs and supplements that support immunotherapy can enhance the immune response, making it more efficient at identifying and attacking cancer cells.
This innovative approach not only helps in treating cancer but also reduces the risk of recurrence, providing a powerful tool in the fight against this disease.
Inflammation is the body’s natural response to injury or infection, but chronic inflammation can contribute to the development and progression of cancer.
Drugs and supplements with anti-inflammatory properties help reduce inflammation, thereby lowering the risk of cancer and other chronic diseases.
By targeting the inflammatory processes, these treatments can help maintain a healthier cellular environment and prevent the conditions that allow cancer to thrive.
