SCIENTIFIC EVIDENCE
Research Insights to Natural Cognitive Support
Feruguard is a dietary supplement combining ferulic acid and Angelica archangelica extract, designed to potentially mitigate and improve age-related cognitive decline. This page reviews the scientific evidence supporting the efficacy, mechanisms of action, and safety of Feruguard, while acknowledging limitations and adhering to scientific empiricism.
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Peer-Reviewed Publications
Clinical and observational studies supporting Feruguard’s formulation.
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Professional Healthcare Endorsements
Recommended by thousands of medical institutions and professionals in Japan.
Key Ingredients and Mechanisms of Action
Ferulic Acid
Ferulic acid (FA), or 3-methoxy-4-hydroxycinnamic acid, is a phytochemical abundant in plant cell walls, particularly in cereal grains. It exhibits significant antioxidant and anti-inflammatory properties, making it a candidate for neuroprotective applications. FA is derived from rice bran and provides both antioxidant and neuroprotective effects.
Mechanisms of Action
Direct Antioxidant Activity:
FA readily forms a resonance-stabilized phenoxy radical, enabling it to scavenge deleterious free radicals and terminate free radical chain reactions. This protects cell membranes from lipid peroxidation.
UV Absorption and Photoprotection:
FA absorbs UV radiation, which catalyzes stable phenoxy radical formation, enhancing its ability to terminate free radical chain reactions. This provides photoprotection to the skin and may alleviate symptoms of photosensitivity disorders.
Modulation of Amyloid Precursor Protein (APP) Processing:
FA has been shown to inhibit β-secretase, an enzyme involved in the production of amyloid-beta (Aβ) peptides, which are major components of senile plaques in Alzheimer's disease (AD). Studies indicate that FA treatment reduces Aβ production and amyloidogenic APP proteolysis in neuron-like cells.
Anti-inflammatory Effects:
FA can inhibit the production of pro-inflammatory cytokines and attenuate neuroinflammation, contributing to neuroprotection.
Upregulation of the Nrf2/ARE Pathway:
Nrf2 Activation:
FA activates the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a critical regulator of cellular antioxidant defenses.
Keap1 Interaction:
Under normal conditions, Nrf2 is bound to Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, which promotes its degradation. Upon exposure to oxidative stress or specific inducers like FA, Nrf2 is released from Keap1.
ARE Binding and Gene Expression:
The released Nrf2 translocates to the nucleus, where it binds to the antioxidant response element (ARE). This binding initiates the transcription of various antioxidant genes.
Heme-Oxygenase 1 (HO-1) Induction:
One of the key genes upregulated by the Nrf2/ARE pathway is heme-oxygenase 1 (HO-1), an enzyme that catalyzes the degradation of heme into biliverdin, carbon monoxide, and ferrous ion. HO-1 possesses potent antioxidant and anti-inflammatory properties.
Inhibition of β-Amyloid Formation:
FA destabilizes preformed beta-amyloid fibrils in vitro.
Improved Bioavailability:
Ferulic acid is more easily absorbed into the body and stays in the blood longer than other phenolic acids.
Angelica archangelica (Garden Angelica)
Angelica archangelica (Garden Angelica) is a biennial plant from the Apiaceae family known for its medicinal properties. Extracts from its roots have been traditionally used for various health benefits, including cognitive enhancement.
Mechanisms of Action
Acetylcholinesterase (AChE) Inhibition:
Angelica archangelica extract inhibits acetylcholinesterase, the enzyme responsible for breaking down acetylcholine, a neurotransmitter crucial for memory and learning. By inhibiting this enzyme, Angelica archangelica can increase acetylcholine levels in the brain, potentially improving cognitive function.
Coumarins and Furanocoumarins:
A. archangelica contains coumarins and furanocoumarins, which are bioactive compounds responsible for its pharmacological activities.
Imperatorin and Xanthotoxin:
The primary furanocoumarins, imperatorin and xanthotoxin, inhibit acetylcholinesterase (AChE). Imperatorin also inhibits both AChE and BChE.
Decursin:
Also found in Garden Angelica, decursin inhibits scopolamine-induced amnesia by inhibiting acetylcholinesterase activity in the hippocampus.
Anti-inflammatory Effects:
Coumarins found in Angelica archangelica may contribute to anti-inflammatory effects.
Antioxidant Properties:
Angelica archangelica can activate the Nrf2 transcription factor and activate the cellular antioxidative defense system.
Neuroprotective Effects:
Extracts and isolated compounds from Angelica gigas (a related species) exert neuroprotective activity by regulating numerous biological processes.
Clinical Evidence of Efficacy
Studies on Mild Cognitive Impairment (MCI)
Kudoh et al. (2020):
A multicenter, randomized, double-blind, placebo-controlled trial investigated Feruguard in participants with MCI. The Feruguard group showed significantly better Mini-Mental State Examination (MMSE) scores at 24 weeks compared to the placebo group (p = 0.041). The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Jcog) scores were also significantly better at 24 and 48 weeks in the Feruguard group (p = 0.035 and p = 0.015, respectively).
Kimura et al. (2014):
An open-label trial with 28 participants with MCI found that daily ferulic acid and Angelica archangelica extract (3.0 g/day) for 96 weeks improved cognitive functions as assessed by the Japanese version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Jcog). The treatment improved ADAS-Jcog scores in 61.1% of the participants.
Studies on Alzheimer's Disease (AD)
Qiu et al. (2022):
A case report of a patient with the frontal variant of Alzheimer's Disease (FvAD) showed the efficacy of Feruguard in treating behavioral and psychological symptoms.
Kimura et al. (2011):
Feruguard treatment led to decreased scores on the Neuropsychiatric Inventory in 19 of 20 patients with frontotemporal lobar degeneration or dementia with Lewy bodies and significantly decreased the score overall. The treatment also led to significantly reduced subscale scores on the Neuropsychiatric Inventory.
Animal Studies
Mori et al. (2013):
In transgenic mice, oral FA treatment reversed transgene-associated behavioral deficits, decreased brain Aβ deposits, reduced β-site APP cleaving enzyme 1 protein stability and activity, attenuated neuroinflammation, and stabilized oxidative stress.
Formulation and Synergistic Benefits
Feruguard contains 200 mg of ferulic acid and 40 mg of A. archangelica extract per daily dose. The combination of these ingredients is designed to provide synergistic benefits, addressing multiple pathways involved in cognitive decline.
Ferulic acid targets oxidative stress, inflammation, and Aβ production.
Angelica archangelica extract inhibits acetylcholinesterase, boosting acetylcholine levels.
Safety
Human Use:
In Japan, over 50,000 people have taken over 1.2 million packages of Feruguard, with no serious adverse events reported.
Clinical trials:
A prospective, open-label trial of daily Feruguard (3.0 g/day) lasting 4 weeks in 20 patients with frontotemporal lobar degeneration or dementia with Lewy bodies found no adverse effects or significant changes in physical findings or laboratory data.
Limitations and Future Directions
While the available evidence suggests potential benefits of Feruguard for cognitive health, several limitations should be considered:
Study Design:
Some studies are open-label, which may introduce bias due to the lack of blinding and a control group.
Sample Size:
Some studies have small sample sizes, limiting the generalizability of the findings.
Further Research:
Further randomized, double-blind, placebo-controlled trials with larger samples are needed to confirm these findings and establish Feruguard as a useful treatment for MCI and related conditions. More research is also required to fully elucidate the mechanisms of action and long-term effects.
FDA Disclaimer
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Please consult with a healthcare professional before starting any new dietary supplement.
References
Bramanti, E., Fulgentini, L., Bizzarri, R., Lenci, F., & Sgarbossa, A. (2013). β-Amyloid amorphous aggregates induced by the small natural molecule ferulic acid. J Phys Chem B, 117, 13816-13821.
Graf, E. (1992). Antioxidant potential of ferulic acid. Free Radical Biology and Medicine, 13(6), 435–448.
Kang, S. Y., & Kim, Y. C. (2007). Decursinol and decursin protect primary cultured rat cortical cells from glutamate-induced neurotoxicity. J Pharm Pharmacol, 59(6), 863-70.
Kimura, T., & Takamatsu, J. (2015). Effect of oral administration of a dietary supplement (feru-guard) containing a mixture of A. archangelica extract and ferulic acid on memory in patients with mild cognitive impairment.
Kimura, T., Hayashida, H., Murata, M., & Takamatsu, J. (2011). Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatrics and Gerontology International, 11, 1-6.
Kudoh, C., Hori, T., Yasaki, S., Ubagai, R., & Tabira, T. (2020). Effects of Ferulic Acid and Angelica archangelica Extract (Feru-guard®) on Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Prospective Trial. Journal of Alzheimer’s Disease Reports, 4(1), 393–398.
Li, L., Du, J.K.; Zou, L.Y.; Wu, T.; Lee, Y.W.; Kim, Y.H. Decursin isolated from Angelica gigas Nakai rescues PC12 cells from amyloid β-protein-induced neurotoxicity through Nrf2-mediated upregulation of heme oxygenase-1: Potential roles of MAPK. Evid. Based Complement. Altern. Med. 2013, 2013, 467245.
Li, L., Du, J., Zou, L., Xia, H., Wu, T., Kim, Y., & Lee, Y. (2015). The neuroprotective effects of decursin isolated from Angelica gigas Nakai against amyloid β-protein-induced apoptosis in PC 12 cells via a mitochondria-related caspase pathway. Neurochem Res, 40(7), 1555-1562.
Mori, T., Koyama, N., Guillot-Sestier, M. V., Tan, J., & Town, T. (2013). Ferulic Acid Is a Nutraceutical β-Secretase Modulator That Improves Behavioral Impairment and Alzheimer-like Pathology in Transgenic Mice. PLoS ONE, 8(2), e55774.
Qiu, G., Xu, C., Guo, Q., & Zhu, F. (2022). Feru-guard Improves Cognitive Dysfunction in the Frontal Variant of Alzheimer's Disease: A Case Report.
Rajendran, P., Nandakumar, N., Rengarajan, T., Palaniswami, R., Gnanadhas, E. N., Lakshminarasaiah, U., Gopas, J., & Nishigaki, I. (2014). Antioxidants and human diseases. Indian Journal of Clinical Biochemistry, 30(1), 11–26.
Sigurdsson S, Gudbjarnason S (2007) Inhibition of acetyl-cholinesterase by extracts and constituents from Angelica archangelica and Geranium sylvaticum. Z Naturforsch C J Biosci 62, 689-693.
Sowndhararajan, K., & Kim, S. M. (2017). Neuroprotective and cognitive enhancement potentials of Angelica gigas Nakai root: A review. Sci Pharm, 85(2), 21.
Yan, J. J., Cho, J. Y., Kim, H. S., Kim, K. L., Jung, J. S., Huh, S. O., Suh, H. W., Kim, Y. H., Song, D. K., & Yan, J. J. (2001). Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol, 133, 89-96.
Zduńska, K., Dana, A., & Kolodziejczak, A., Rotsztejn, H. (2018). Antioxidant Properties of Ferulic Acid and its Possible Application. Skin Pharmacology and Physiology, 31, 332–336.