Ellagic acid side effects, benefits, use for cancer, review of research
October 26 2016 by Ray Sahelian, M.D.

Ellagic acid, a phenolic acid is found in berries (raspberries, strawberries), pomegranate, grapes, and nuts acts as an antioxidant. It has shown positive attributes in esophageal and colon cancer in animals studies and possibly prostate cancer. Human studies are limited but show it to have some potential in cancer prevention or treatment.

Purchase ellagic acid in Pomegranate 500 mg, 60 Capsules
The fruit of the Punica granatum (pomegranate) contains hundreds of phytochemicals and pomegranate extracts have recently been shown to exhibit antioxidant properties, thought to be due to the action of ellagic acid, the main polyphenol in pomegranate.

Get the benefits of the juice and avoid all the calories and sugar (fructose).

Supplement Facts: Pomegranate extract 500 mg

Purchase Ellagic acid supplement in Pomegranate product
Source Naturals, Ellagic Active, 300 mg, 60 Tablets

Recommendation: Take 1 or 2 capsules daily with food or water.

Q. Can you tell me how much ellagic acid is found in pomegranate juice? Also what are punicalagins?
  A. There are variations in content in various pomegranate juice products depending on where the pomegranate is grown. We found one study where a person was given 180 ml (about 6 ounces) of pomegranate juice, and there apparently was ellagic acid 25 mg and hydrolyzable ellagitannins 318 mg, as punicalagins, the major fruit ellagitannin.

You may also consider other healthy herbs and supplements with high antioxidant potential, including acai berry supplement, cacao extract, curcumin supplement, goji berry extract, graviola fruit, mangosteen and noni fruit extract.

Role in plants
Ellagic acid is found in plants in the form of ellagitannin, a combination of ellagic acid and glucose. It is believe that many plants use this substance to protect themselves against infection or destruction by germs and other organisms.

How is it available?
Ellagic acid is sold in capsule and powder form. You can also find a high ellagic content in pomegranate extract.  Many herb and vitamins ingredient suppliers sell pomegranate at various extract potencies. Some of these include pomegranate extract at 20 percent ellagic acid, pomegranate extract at 40 percent, and pomegranate extract at 70 percent.

Adv Nutr 2016. Improvements in Metabolic Health with Consumption of Ellagic Acid and Subsequent Conversion into Urolithins: Evidence and Mechanisms. Ellagic acid (EA) is a naturally occurring polyphenol found in some fruits and nuts, including berries, pomegranates, grapes, and walnuts. EA has been investigated extensively because of its antiproliferative action in some cancers, along with its anti-inflammatory effects. A growing body of evidence suggests that the intake of EA is effective in attenuating obesity and ameliorating obesity-mediated metabolic complications, such as insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this review, we summarize how intake of EA regulates lipid metabolism in vitro and in vivo, and delineate the potential mechanisms of action of EA on obesity-mediated metabolic complications.

Although the early research is promising, we need many more long term studied to determine whether it plays a role in cancer prevention or treatment.

The Journal of Nutritional Biochemistry. 2004.
In vitro anti-proliferative activities of ellagic acid.
The potential cytotoxic and anti-proliferative activities of ellagic acid was evaluated using human umbilical vein endothelial cells (HUVEC), normal human lung fibroblast cells HEL 299, Caco-2 colon, MCF-7 breast, Hs 578T breast, and DU 145 human prostatic cancer cells. Ellagic acid at concentration in the range 10-100 micromol/L did not affect the viability of normal fibroblast cells during a 24-hour incubation. An increase in adenosine triphosphate (ATP) bioluminescence of approximately 18-21% was observed in normal cells incubated with ellagic acid. In contrast, ellagic acid dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. Ellagic acid induced cancer cell death by apoptosis. It was also observed that the mechanism of apoptosis induction in ellagic acid-treated cancer cells was associated with decreased ATP production, which is crucial for the viability of cancer cells.

Bladder cancer
Ellagic acid induced p53/p21 expression, G1 arrest and apoptosis in human bladder cancer T24 cells.
Anticancer Res. 2005.
It is well known that dietary phenolic compounds can elicit vital cellular responses such as cytotoxicity, cell cycle arrest and apoptosis by activating a cascade of molecular events. Ellagic acid is one of these phenolic compounds, but the exact mechanism of its action is still unclear. The objective of this study was to investigate ellagic acid-induced cell cycle arrest and apoptosis in T24 human bladder cancer cells in vitro. Assays were performed to determine cell viability, cell cycle arrest, apoptosis, caspases-3 activity and gene expression, measured by flow cytometric assay, polymerase chain reaction (PCR) and determination of caspase-3 activity. Ellagic acid significantly reduced the viable cells, induced G0/G1-phase arrest of the cell cycle and apoptosis. Ellagic acid also increased p53 and p21 and decreased CDK2 gene expression, that may lead to the G0/G1 arrest of T24 cells.

Breast cancer
Asian Pac J Cancer Prev. 2014. Ellagic Acid Exerts Anti-proliferation Effects via Modulation of Tgf-β/Smad3 Signaling in MCF-7 Breast Cancer Cells.

Leukemia treatment or prevention
Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells.
Cancer Lett. 2005.
Anticarcinogenic effects of polyphenolic compounds in fruits and vegetables are well established. Although polyphenols naturally occur as combinations, little information is available regarding possible synergistic or antagonistic biochemical interactions between compounds. Identifying potential interactions between polyphenols may provide information regarding the efficiency of polyphenol-containing foods in cancer prevention. The objective of this study was to investigate the interactions of ellagic acid and quercetin with resveratrol, polyphenols which occur in muscadine grapes, with the hypothesis that the selected polyphenols would interact synergistically in the induction of apoptosis and reduction of cell growth in human leukemia cells (MOLT-4). To test this hypothesis, alterations in cell cycle kinetics, proliferation, and apoptosis (caspase-3 activity) were examined after incubation with ellagic acid, quercetin, and resveratrol as single compounds and in combination. Results showed a more than additive interaction for the combination of ellagic acid with resveratrol and furthermore, significant alterations in cell cycle kinetics induced by single compounds and combinations were observed. An isobolographic analysis was performed to assess the apparent synergistic interaction for the combinations of ellagic acid with resveratrol and quercetin with resveratrol in the induction of caspase 3 activity, confirming a synergistic interaction with a combination index of 0.64 for the combination of ellagic acid and resveratrol and 0.68 for quercetin and resveratrol. Results indicate that the anticarcinogenic potential of foods containing polyphenols may not be based on the effects of individual compounds, but may involve a synergistic enhancement of the anticancer effects.

Prostate cancer
Prostate. 2015. Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis.

Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate.
Eur Urol. 2005.
Recent phase III studies in hormone refractory prostate cancer (HRPC) showed an improvement in terms of overall survival, objective response (OR) and biochemical response (BR); however, chemotherapy is usually accompanied by negative side effects that determines poor quality of life and only marginally improves individual clinical response (ICR) in terms of pain relief and performance status. Ellagic acid is a polyphenol that is found in many species of flowering plants. It is an antioxidant that determines apoptosis, down regulation of IGF-II, mediates the cumulative effect on G1/S transition phase and prevents destruction of p-53 gene by cancer cells. The aim of this study was to assess the effects of ellagic acid support therapy on toxicity, OR, ICR and BR in HRPC patients treated with estramustine phosphate and vinorelbine. Patients with HRPC were randomly distributed in two study groups: a control group (group A) who underwent chemotherapy with vinorelbine and estramustine phosphate, and an experimental group (group B) where chemotherapy regimen was associated with ellagic acid. A reduction in systemic toxicity, statistically significant for neutropenia, associated with better results in term of OR rate, ICR, and BR were observed in group B compared with group A. On the contrary no significant difference in OS and PFS was detected between groups. Our study suggests that the use of ellagic acid as support therapy reduces chemotherapy induced toxicity, in particular neutropenia.

Does it help with maintaining healthy blood sugar levels?
   We are not sure.

HIV infection
Indian J Med Res. 2013. Ellagic acid and gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity. Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. The active components responsible for anti-HIV activity were gallic acid and ellagic acid, through inhibition of reverse transcriptase and HIV protease, respectively and hence could be regarded as promising candidates for the development of topical anti-HIV-1 agents.

Nerve protection, memory, dementia, cognitive decline
Pharm Biol. 2016. Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments. In a previous study, it has been shown that ellagic acid, a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms. This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals' locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons.