Healthy Aging

Health Benefits of Grapefruit Seed Extract

A natural antimicrobial and antioxidant with apparent anti-aging effects

Grapefruit, also known as Citrus paradisi, is a hybrid fruit that originated centuries ago as a natural cross between sweet orange and pomelo.[1] While the seeds of the grapefruit are not typically eaten, grapefruit seed extract (GFSE) is increasingly being used as a dietary supplement, owing to its health-promoting effects.

In this article we review the health benefits of grapefruit and grapefruit seed extracts, and the importance of seeking a high-quality supplement.

Citrus fruits are particularly abundant in flavonoids, particularly in their skin and seeds. Flavonoids may account for up to 75% of the total solids.[2] Grapefruit contains over 25 different flavonoids,[3] with the predominant one being naringin,[4] a glycoside that gives grapefruit its bitter taste and many of its health benefits.[5],[6],[7],[8]

When naringin is ingested, it is converted by the intestinal microflora to the active metabolite naringenin,[9],[10],[11] which is readily absorbed and exerts biological effects throughout the body.[12],[13],[14] (The terms naringin and naringenin are used somewhat interchangeably, because naringin is the substance that is consumed, but naringenin is the bioactive form in the body.)

Naringin may protect the heart, brain, lungs, and other organs against age-related deterioration.

While GFSE and naringin are most known for their antimicrobial properties, studies suggest that grapefruit products containing naringin might also help prevent and treat metabolic syndrome,[15],[16],[17],[18] cardiovascular diseases,[19],[20] and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.[21],[22],[23],[24] Moreover, naringin may protect the heart, brain, lungs, and other organs against age-related deterioration.[6],[19],[25]

These new discoveries have prompted a surge of interest in GFSE as a preeminent source of naringin.

Antimicrobial properties of grapefruit seed extract

GFSE has strong antimicrobial activity and is capable of deactivating or destroying food-borne and opportunistic pathogens on surfaces such as kitchen counters, medical catheters, and even the skin.[8],[26],[27] GFSE has been shown to strongly inhibit the growth of pathogenic bacteria, including Pseudomonas, Salmonella, Escherichia coli, Enterococcus and Staphylococcus species.[28],[29],[30],[31] For these reasons, GFSE has been intensively studied as a preservative for fresh fruits and vegetables.[8]

GFSE has been shown to strongly inhibit the growth of pathogenic bacteria.

One species of bacteria that can be inhibited by GFSE is Staphylococcus aureus, the leading cause of skin and soft tissue infections, which also can cause pneumonia, joint infections, and urinary tract infections (UTIs). S. aureus is notorious because it forms antibiotic-resistant biofilms, which are slimy films containing clumps of bacteria surrounded by a polymeric matrix that sticks to surfaces, making it difficult to disrupt. However, GFSE may do the trick: it was recently reported to inhibit S. aureus living within biofilms, and to inhibit the formation of the biofilm matrix as well.[32]

Consistent with these findings, case studies suggest that grapefruit seeds may be useful for the treatment of UTIs, which can be caused by S. aureus, as well as many other microbes which GFSE potentially inhibits.[33] Additionally, GFSE has been found to inhibit Candida albicans, the most common human yeast infection.[34],[35] In one study, GFSE reduced the viability of biofilm-forming C. albicans by more than 90%.[35] GFSE also was found to inhibit bacteria that cause periodontal disease, namely Porphyromonas gingivalis,[36] suggesting that GFSE may be useful as a component of toothpaste or mouthwash.

Laboratory investigations further suggest that naringin might be effective against influenza virus,[37] hepatitis C virus (HCV),[38] and several other viruses that infect humans.[39],[40],[41] Based on chemical modeling, two independent research groups recently predicted that naringin can bind to the angiotensin-converting enzyme 2 (ACE2) receptor, which plays a role in inflammatory and certain infectious lung diseases.[42],[43],[44] Of six different citrus flavonoids, naringin was predicted to have the highest binding affinity to ACE2.[42] Of course, clinical studies are needed to confirm these intriguing findings.

Along with their antimicrobial properties, naringin and naringenin exhibit potent anti-inflammatory effects, which may help prevent the flood of cytokines that can accompany respiratory infections and damage the lungs.[42] In animal studies, supplementation with naringin and naringenin has been shown to reduce the lung inflammation that occurs with asthma, pulmonary fibrosis, and cigarette smoking.[45],[46],[47],[48],[49] This suggests that naringin may not only help fight respiratory infections, but may also more broadly promote lung health.

Grapefruit seed extract for metabolic syndrome

Metabolic syndrome is dramatically increasing around the world. The conditions associated with the term metabolic syndrome include excess belly fat, elevated blood pressure, insulin resistance, and abnormal blood glucose and cholesterol levels (hypercholesterolemia). Metabolic syndrome tends to creep up gradually with age, and typically doesn’t resolve on its own.[50] Individuals with metabolic syndrome have an elevated risk for heart disease and stroke, so it is important to address the problem at an early stage.[51]

The consumption of fruit flavonoids may help prevent or slow the development of metabolic syndrome.[19],[20] The consumption of one red grapefruit daily for 30 days, for example, was shown to reduce serum triglyceride and cholesterol levels in patients with atherosclerosis (a buildup of cholesterol plaque in the walls of arteries.)[52] The results of several randomized clinical trials, as well as population studies, have demonstrated a correlation between grapefruit intake and lower blood pressure and waist circumference in adults.[53],[54],[55] These benefits are likely to be due to naringin.

Animal studies provide further evidence that the consumption of citrus flavonoids may help lower blood cholesterol, triglycerides, and inflammatory markers.[56],[57] In mice genetically predisposed to insulin resistance and high cholesterol (hypercholesterolemia), supplementation with a mixture of citrus flavonoids or with naringenin itself was shown to reduce plasma cholesterol and triglyceride levels and restore insulin sensitivity.[58],[59] Naringin supplementation also ameliorated the signs of metabolic syndrome in animals with diet-induced hypercholesterolemia, insulin resistance, and/or obesity.[60],[61],[62],[63] Supplementation with naringin also prevented the development of atherosclerosis in two of these studies.[60],[61]

Naringin supplementation may help reduce blood glucose, cholesterol, and/or triglyceride levels.

Supporting these pre-clinical animal results, several preliminary human studies suggest that naringin supplementation can reduce blood glucose, cholesterol, and/or triglyceride levels.[64] In one clinical study of adults with high blood cholesterol levels, the administration of naringin (400 mg per capsule per day) for eight weeks lowered plasma total cholesterol levels by 14%.[65]

The incidence of metabolic syndrome increases with menopause in women, thus increasing the risk of cardiovascular disease.[66] In a mouse model of menopause, supplementation with naringenin helped lower fasting blood glucose and insulin levels, and reduced belly fat by over 50% compared to controls.[67] Additionally, in a clinical trial in healthy menopausal women, the consumption of grapefruit juice (340 milliliters per day, equivalent to 1.4 cups) reduced arterial stiffness after 6 months.[68] (Arterial stiffness is an indicator of atherosclerosis.)[69] This anti-atherogenic effect of grapefruit juice is consistent with population studies showing that high intakes of citrus flavonoids are associated with a lower risk of cardiovascular disease and stroke.[56],[70],[71] Therefore, the consumption of citrus fruits and GFSE may be particularly helpful for postmenopausal women.

Grapefruit seed extract for the heart, brain, and skin

Naringenin may protect heart cells and other tissues against aging by activating Nrf2, the master regulator of antioxidant responses in the body.[72],[73] In addition to its antioxidant effects, naringenin has been shown to activate Sirtuin 1 (SIRT1), a cellular enzyme that is a hot target for anti-aging research.[74] The level of SIRT1 declines with age, and this decline is implicated in insulin resistance, diabetes, non-alcoholic fatty liver disease, and heart disease.[75],[76] In studies of aged mice, the administration of naringin for six months enhanced SIRT1 expression in heart muscle and suppressed fibrotic remodeling, a factor that plays a role in heart disease.[74]

Naringenin also was shown to extend the life span and healthspan of the nematode Caenorhabditis elegans[77] (also known as “the worm”),[78] an organism that serves as a model for the study of human aging.[79] The study showed that naringenin regulated specific anti-aging genes and helped protect against the damaging effects of ultraviolet light.[77] Additional studies showed that naringenin could suppress photoaging in human skin cells,[80] and it even reduced wrinkles in hairless mice exposed to skin-damaging ultraviolet light.[81]

Naringenin may help neurons to survive under conditions of aging, inflammation, and/or injury.

Naringenin may also support brain health by reducing oxidative stress, both by activating Nrf2[82] and by helping neurons to survive under conditions of aging, inflammation, and/or injury.[83],[84],[85],[86] Consistent with these findings, naringin was shown to improve learning and memory in animal models of Alzheimer’s disease,[87],[88],[89],[90] and to prevent the loss of dopamine-producing neurons in animal models of Parkinson’s disease.[25],[86],[91]

Last but not least, supplementation with naringin has been shown to protect the heart, kidneys, lungs, and brain against the toxic effects of chemotherapy in animal models.[92],[93],[94] It even was shown to prevent behavioral changes associated with chemotherapy treatment, thus suggesting that naringin might help protect against “chemo brain.”[93],[95]

Safety and efficacy of grapefruit seed extracts

It is important to choose a GFSE supplement that has undergone third-party testing to ensure that the product is free of contaminants.

GFSE, which provides naringin, is a promising natural product for the support of overall health and for addressing diseases of aging. While optimal doses of naringin have not yet been determined, one study suggests that effective plasma concentrations of naringenin may be provided by drinking one to four cups of grapefruit juice per day,[57] while another group estimates that two to three liters (8 to 12 cups) may be required.[96] It may be more practical and efficient to supplement with GFSE to obtain the benefits of naringenin.

Although citrus is typically a health-friendly food, it’s worth noting that citrus extracts naturally contain furanocoumarins,[97] compounds that can affect the body’s metabolism of many different medications and increase the risk of side effects.[98] Pharmacists therefore often recommend that patients avoid consuming grapefruit juice while taking prescription medications.

Some untested GFSE supplements have been found to contain potentially dangerous contaminants such as triclosan, benzethonium chloride, and benzalkonium chloride.[99],[100] It is therefore important to choose a GFSE supplement that has undergone third-party testing to ensure that the product is free of contaminants, as well as soy, dairy, and gluten.

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