Nutrition is important! Florida Orange Juice has several nutrients and plant compounds that are part of a healthy, balanced diet for brain health: Flavonoids, such as hesperidin Vitamin C Thiamin vitamin B1 Vitamin B6 Florida Orange Juice provides more nutrition than you may expect.

The nutrients in Florida Orange Juice are being studied for their role in brain health and cognition. References Canadian Food Inspection Agency , May 11 : Nutrient Function Claims.

Am J Clin Nutr. Alharbi et al. Eur J Nutr. Nurk et al. Br J Nutr. Lamport et al. Yuan et al. Spencer et al. Mol Aspects of Med. Jaeger et al. Mol Aspects Med. Carb counting is complicated. Take the quiz and test your knowledge!

Together with her husband, Kansas City Chiefs MVP quarterback Patrick Mahomes, Brittany Mohomes shares how she parents two children with severe food….

While there are many FDA-approved emulsifiers, European associations have marked them as being of possible concern. Let's look deeper:.

Researchers have found that a daily multivitamin supplement was linked with slowed cognitive aging and improved memory. Dietitians can help you create a more balanced diet or a specialized one for a variety of conditions.

We look at their benefits and limitations. Liquid collagen supplements might be able to reduce some effects of aging, but research is ongoing and and there may be side effects.

A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Nutrition Evidence Based 9 Intriguing Benefits of Tangerines. Medically reviewed by Kathy W. Warwick, R. Packed with nutrients. High in antioxidants. Immunity boosters.

May support brain health. Could help improve skin appearance. May support heart health. May have anticancer properties. Easy to add to your diet. The bottom line. Just one thing Try this today: Follow this easy marmalade recipe to avoid wasting overripe tangerines.

Was this helpful? How we reviewed this article: History. Sep 6, Written By Ariane Lang. Share this article. Read this next. By Anne Danahy, MS, RDN. In a review of three studies, research showed that grapefruit juice increased the risk of urinary stones, while orange juice decreased the risk.

However, smaller prospective clinical studies did not demonstrate an increased risk with grapefruit juice. Researchers suspect citrus fruit juices may be protective because of their citrate content, which is one of the strongest inhibitors of stone formation.

Some evidence suggests citrus fruits may have a protective effect on cancer. Specifically, that citrus fruit was negatively associated with the following types of cancer:.

However, researchers did not note an adverse risk associated with prostate cancer and even found a positive correlation with that type of cancer. Research has found that citrus fruits have protective effects against heart disease.

Specifically, the flavonoids in citrus fruits protect against:. As a result, researchers have found that these citrus flavonoids are associated with improved cardiovascular heart outcomes. Flavanones in citrus fruits may have neuroprotective potential.

One study found citrus fruits may have a protective effect against the following:. While not entirely established, researchers say emerging human studies indicate future potential. While citrus fruits probably won't prevent you from catching a cold entirely, they may help your immune system fight it faster, thanks to the high vitamin C content.

The severity of symptoms was also reduced. Whether you consume it juiced or whole, citrus fruits provide good hydration. In addition, due to their high vitamin C content, they help you absorb foods with iron. Therefore, pairing citrus and high-iron foods can help your body make the most of these nutrients.

While citrus fruits' benefits are plentiful, there are some risks associated with citrus fruits. The high acid content and sweetness can be a bad combination for tooth enamel. Try not to go overboard with citrus fruits; and when you do eat or drink them, brush your teeth well afterward.

Grapefruit and its juices can interfere with how some medications work. That's because many drugs are metabolized by an enzyme called CYP3A4. Grapefruit juice can block this process in the intestines resulting in too much of the drug entering your body.

Examples of medications that interact with grapefruit include certain types of the following medications:. Since the list of medications is extensive, if you take any prescriptions, ask your healthcare provider about possible interactions before consuming grapefruit.

As with other fruits, the best way to consume citrus is whole rather than juiced. That's because when fruits are juiced, they are absorbed more quickly, leading to a faster spike in blood sugar. One study found that consuming fruit juices was associated with an increased risk of type 2 diabetes.

Some people are allergic to citrus fruit. While uncommon, citrus allergies are possible. Citrus allergy symptoms are the same as others and may include itching skin or mouth, runny nose, and sneezing. More serious life-threatening allergies, called anaphylaxis , can also occur.

This life-threatening emergency includes wheezing , shortness of breath, and a feeling of doom. If you notice these symptoms, seek medical attention immediately. Citrus fruits include oranges, lemons, limes, and grapefruit, among others. They contain high levels of vitamin C, flavonoids, potassium, and fiber.

Their antioxidant, anti-inflammatory, and immune-boosting properties have been associated with health benefits, like protection from heart and brain disease, cancer, kidney stones, and reducing the length of a cold. Some people should be careful with citrus fruit, especially those with a citrus allergy or who take certain medications.

Food and Agriculture Organization of the United Nations. Markets and trade: Citrus. Department of Agriculture. Orange, raw. National Institutes of Health: Office of Dietary Supplements. Vitamin C: Fact sheet for health professionals. Lv X, Zhao S, Ning Z, et al.

Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.

You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.

In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The cognitive-protective effects related to the consumption of a variety of fruits are supported by several intervention studies. PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until February, Cognition was tested by global or domain specific tasks.

Out of 13, articles identified, 16 papers were included; 11 studies provided suitable data for meta-analysis. Fourteen studies reported improvement or trend for improvement in cognition, five studies assessed mood and one study supplementing grape juice found trend for mood improvement. The meta-analysis did not sufficiently support a role for fruits or fruit forms to improve cognition and mood.

Age-induced cognitive decline is a common and important phenotype that is likely to be associated with increased disease risks such as dementia [ 1 ]. Ageing is associated with an increased susceptibility to chronic organ disease and decline of metabolic and immune functions which impact on the brain [ 1 ].

Therefore, the measurement and treatment of cognitive impairment is important due to the rising prevalence of dementia [ 2 ] and the benefits of early detection and prevention [ 3 ]. The rate of age-related cognitive impairment is mainly influenced by lifestyle behaviours, including diet [ 4 , 5 ].

Fruits and vegetables represent a rich source of antioxidants including vitamins vitamin C, B complex and E etc. A number of potential underlying mechanisms have been identified including the interaction of fruit polyphenols, carotenoids and vitamins with intracellular neuronal and glial signalling pathways, regulation of cerebral blood flow, and protection against neurotoxins and neuroinflammation [ 8 , 9 , 10 ].

A number of intervention studies also showed positive results indicating that intake of a range of flavonoid-rich fruit e. blueberry, orange juice improves both immediate and chronic cognitive performance or mood in older adults [ 12 ]. From a nutritional perspective, employing single whole foods instead of single components such as a supplement in interventions is more appropriate since synthetic single nutrient supplements are likely to be metabolised through different pathways to natural bioactive compounds [ 13 ].

Fruit can be consumed in a variety of forms following different processing methods, for example as fruit juices, smoothies, frozen fruit, and freeze-dried fruit powders and a recent paper emphasized the need for additional research assessing the effect of processed fruit on health, as fruit in processed forms e.

processed powder provide consumer options whilst also reducing costs and food waste [ 14 ]. These different fruit forms could be an effective method to increase overall fruit consumption and it is important to determine the impact of different fruit groups and delivery forms on cognition in order to better inform the public.

Therefore, the protective effects on cognition of whole fruit intervention or fruit intervention in different forms e. powder, juice instead of single molecules, such as polyphenols, are worth exploring. Inconsistent findings have been reported on fruit interventions for cognitive effects [ 15 , 16 ].

Whilst small sample size is indicated as a factor in null findings, the length of intervention as well as type and form of fruit may also be important.

There could be metabolic difference between acute and chronic polyphenol-rich fruit interventions. Emerging evidence from acute interventions employing a range of fruit juices and dried powders also indicates that polyphenol-rich fruit-based interventions e.

citrus, grape, and blackcurrant juice and powder may benefit brain function [ 20 , 21 , 22 ]. In terms of nutritional value, fruit juices and dried fruit powders retain polyphenols, vitamins and minerals that are bio-accessible despite fibre and other nutrient losses that occur during processing [ 23 , 24 ].

Fruit processing, such as smashing or thermal treatment, can damage the cell structure of whole fruit releasing cytoplasmic content that can make bioactive compounds more accessible for absorption [ 25 ].

Moreover, the presence of other constituents formed from the technological process or added from food matrix such as sugar could modify the bioavailability of the bioactives due to their ability to bind, solubilize, or stabilize [ 26 ]. Research has explored the difference in nutritional value and bioavailability of bioactives between whole fruit and processed fruit.

Furthermore, Kuntz et al. compared the bioavailability of selected anthocyanins from grape and blueberry juice with a smoothie and found no difference in plasma pharmacokinetics and recovery of the major anthocyanin species. However, significantly higher concentrations of the phenolic acid 3,4-dihydrobenzoic acid were shown after ingestion of the juice [ 28 ].

It is also worth noting that the cognitive domains categorised in intervention studies often vary depending on the cognitive ability that researchers intend to assess with different tasks applied [ 26 ].

Therefore, the impact of fruit interventions on specific cognitive domains cannot be quantitatively compared because of the large variability in the assessment tools and scoring interpretations. This concern has also been highlighted in other dietary trials assessing cognition [ 29 ].

Due to the impact of mood on cognition, we also included assessment of mood outcomes here [ 30 ]. We searched for studies investigating the effect of berry, cherry and citrus fruit supplementations on cognition and mood. Berries so defined includes grapes, blueberries, strawberries etc; citrus includes oranges etc; cherry is categorised as stone fruit [ 31 ].

their juices to be consumed without acute supplementation prior to testing; 4 control: control groups without components of citrus, cherry, or berries, likely isoenergetic placebo group; 5 outcomes: cognitive function and mood described below ; 6 Only English-language and peer-reviewed articles were included.

No restriction of publication year was applied. This review is in line with the PICOS population, intervention, comparator, outcome, study design framework Supplemental Table 1. The systematic review was conducted with a prospective protocol in accordance with Cochrane Handbook for Systematic Reviews of Interventions version 5.

The protocol was registered with PROSPERO, the International Prospective Register of Systematic Reviews Registration number CRD This protocol includes the investigation of the impact of these fruits on the risk factors of cardiovascular diseases, however the analysis has been reported elsewhere [ 35 ].

The search started from inception until February using PubMed, Web of Science, Scopus and psycARTICLES. Full electronic search strategy for PubMed was added in Supplemental Table 3.

Two researchers YW and JLG assessed articles independently for inclusion eligibility. All records were exported to EndNote X8 reference management software. Articles were moved to the next screening phase or discarded when full disagreement was reached.

Any disagreements that were not resolved were handled by CHR and JKL serving as arbitrators. No disagreements occurred during the selection phase. The selection of eligible studies was based on 2 steps. Firstly, the title and abstract of each study was screened for relevance; full texts were then reviewed for those with potential for inclusion.

Reference lists of included papers and relevant systematic reviews were also supplemented by hand-searching for additional articles. Data were extracted by YW and JLG independent of each other, their selections for accuracy were reviewed in meeting.

Corresponding authors were contacted via e-mail for requested information if there was missing data or for clarification. A pre-defined data extraction form was used to input study data, which includes information on 1 author and published year; 2 study design; 3 population characteristics ethnicity, mean age, sex, mean BMI, health status and sample size at baseline ; 4 treatment details intervention type, length, dosage and frequency ; 5 control group settings; 6 retention rate; 7 measured cognitive testing scores for both experimental group and placebo group at baseline and the longest post-intervention time point to avoid the bias of selectively choosing data if applicable ; 8 recording any data adjustments made for physical activity level among the included studies.

Primary outcomes of the analyses were cognitive and mood scores after intervention and placebo treatment. The cognitive function measured in each study was categorized into memory, executive function and psychomotor speed domains for meta-analysis.

The domain categorization in this review was based on a commonly used approach to understand cognitive domains [ 36 ]. Study quality was assessed by Cochrane Risk of Bias RoB2 tool with assessment of five components, D1 of randomisation process, D2 of deviations from intended interventions, D3 of missing outcome data, D4 of measurement of the outcome and D5 of the selection of the reported results [ 29 ].

The overall risk of study bias was rated by low risk, some concerns or high risk. Grading of Recommendations Assessment, Development, and Evaluation GRADE evidence profile [ 37 ] was also applied to evaluate the risk of bias, inconsistency, indirectness, and imprecision of evidence in the aspects of assessed executive function, memory, psychomotor speed and mood in the RCTs included in the present review.

R studio version 3. However, insufficient study data was obtained to implement subgroup analysis to further explore the impact of the variations induced by study design and participant characteristics. As shown in Table 1 , based on the categorised cognitive tasks, meta-analyses investigating the effects of berry interventions on memory, executive function and psychomotor speed [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and 2 cherry juice studies assessing executive function and psychomotor speed were carried out [ 41 , 50 ].

Two grape powder studies assessing MMSE Mini Mental State Examination , which measures cognitive impairment, were also included [ 51 , 52 ].

Standard deviation of mean difference SMD was used for studies assessing MMSE, memory, executive function, and psychomotor speed, where studies used different assessments or different measurement units. In accordance with PRISMA guidelines [ 34 ], the selection process for included studies is shown in Fig.

The initial search produced 14, articles from the four databases, no additional article was added from manual search through reference lists of articles previously identified. This record was reduced to articles after duplicates were removed. After screening of titles and abstracts for eligibility, articles were excluded either due to not being human intervention studies or abstract only.

The final selection identified 23 trials assessing cognition, seven articles were further excluded after checking full-text eligibility.

Sixteen trials were included in this review, 11 trials from these were included in the meta-analysis. Among 16 included studies in this review Table 2 , there were 3 crossover RCTs [ 43 , 57 , 58 ] and 13 parallel RCTs [ 41 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 59 , 60 , 61 ].

The average age of the participants in the interventional and control group for included studies were Thirteen of these studies recruited older participants aged 60 years or older [ 41 , 44 , 45 , 46 , 47 , 48 , 50 , 51 , 52 , 57 , 59 , 60 , 61 ].

Baseline characteristics of participants varied across interventions, 10 studies included healthy participants at baseline [ 41 , 43 , 44 , 45 , 47 , 49 , 51 , 57 , 58 , 61 ], five studies included older people manifesting cognitive decline [ 46 , 48 , 52 , 59 , 60 ] and the remaining one study recruited diagnosed mild to moderate dementia [ 50 ].

There were 9 studies supplementing fruit juice and concentrate [ 41 , 43 , 44 , 45 , 50 , 57 , 58 , 59 , 60 ], six studies supplemented fruit powder [ 46 , 48 , 49 , 51 , 52 , 61 ] and only one study used whole frozen fruit [ 47 ].

Among 16 studies, the mean intervention duration was 13 weeks, ranging from 1 week to 6 months. Two studies supplementing Aronia melanocarpa berry and grape powder used placebo powder composed of maltodextrin as control [ 49 , 62 ]. The rest of the studies used placebo beverage or powder matched for energy, carbohydrate, flavour but devoid of polyphenol content as a control [ 41 , 43 , 44 , 46 , 58 , 59 , 60 , 64 , 48 ].

Three studies supplemented blueberry powder with mean dosage of For example, Lee et al. supplemented grape powder that was comparable to three servings of fresh grapes daily approx.

Two studies supplementing blueberry powder were equivalent to providing one cup and 1. Ahles et al. Schrager et al.

Figure 2 presents the RoB2 assessment for each study. Eleven studies presented low risk in the evaluation of randomisation process and five studies presented some concerns.

Seven studies presented low risk in the evaluation of deviations from intended interventions, eight studies presented some concerns, and one study presented high risk. Six studies presented low risk in the evaluation of missing outcome data, 10 studies presented some concerns.

Seven studies presented low risk in the measurement of the outcome, eight studies presented some concerns and one study presented high risk. All 16 studies presented low risk in the selection of the reported result.

Six studies presented low risk for overall study risk of bias, nine studies presented some concerns for overall study risk of bias and one study presented high risk for overall study risk of bias.

As summarised in Table 2 of GRADE evidence, there may be serious risk of bias in the assessment of executive function, memory and psychomotor speed in the RCTs included in this review.

The risk of bias in the assessment of mood and the risk of inconsistency, indirectness, or imprecision of the assessment of executive function, memory, psychomotor speed and mood was not serious in the RCTs included in this review.

As shown in Table 3 , all 16 included studies have assessed cognition with 14 studies reporting improvement or trend for improvement in cognition; 10 studies also assessed mood and one study supplementing grape powder found trend for mood improvement.

For blueberry powder supplementations, Boespflug et al. reported no effect on cognition and mood as assessed by the Positive and Negative Affect Schedule-NOW [ 61 ]. For grape powder supplementation, Calapai et al. For grape juice supplementations, Lamport et al. reported attenuated cognitive error 5.

For cherry juice supplementations, Chai et al. Kent et al. Morehen et al. found no significant changes in assessed sleep, fatigue or mood between pre- and post-intervention and between groups [ 58 ].

Studies incorporating grape juice, grape powder, blueberry juice, blueberry powder, cranberry juice and frozen blueberry constituting a berry group along with studies supplementing cherry juice were able to provide sufficient data to run meta-analysis. There was insufficient data for mood to be entered into meta-analysis, but the mood assessment results for individual studies are reported in Table 3.

As shown in Fig. Forest plot of a berry studies and b cherry juice studies assessing psychomotor speed. Forest plot of a berry studies and b cherry juice studies assessing executive function.

There was no change of heterogeneity in executive function and psychomotor speed assessment after the sensitivity analysis excluding studies applying physical activity adjustments and supplementing concentrate, the sensitivity analysis also suggested no effect of physical activity level and juice quality on the interventional effect Table 4.

Trim and fill method was further implemented to adjust for publication bias Supplemental Fig. However, it is important to note that only two studies were included and one of those had a high risk of bias [ 41 ], which limits the impact of this finding.

Our meta-analyses suggested no differences between the intervention and control groups in any cognitive domains following berry or other fruit-based supplementations.

No improvement was observed on any outcomes including executive function and memory, which does not support the notion that the consumption of specific fruit powders or other fruit juices will confer a cognitive-protective benefit.

Overall, the individual interventions showing improvements in our systematic review still require further substantiation given that the meta-analysis only suggests that cherry juice may have cognition-protective potential.

The systematic review suggested the potential for whole blueberries, blueberry juice concentrate, blueberry powder, grape powder, grape juice, cherry juice, orange juice and cranberry juice supplements to improve cognitive health.

Supplementing grape juice also showed potential to improve mood. However, from the meta-analysis, we only found a borderline significant improvement in psychomotor speed following chronic consumption of cherry juice.

In our review, grape powder and juice interventions have shown improvement to cognition or mood for at least one of the cognitive aspects [ 43 , 52 , 59 , 60 , 62 ]. Studies supplementing blueberry powder, cherry juice and cranberry juice also have reported effect on cognitive or mood benefit [ 46 , 48 , 50 , 64 , 69 , 70 ].

However, the anthocyanin profile in polyphenol-rich fruit is a factor explaining variability in the biological responses observed in dietary interventions with this fruit. For instance, blueberries contain primarily delphinidin, malvidin, and petunidin whereas raspberries and blackberries contain primarily cyanidin, pelargonidin and malvidin [ 71 ].

The rate of polyphenol absorption from blueberries could be influenced by dose administered [ 74 ], and the matrix of the food source [ 75 ], and several studies have suggested that the rate of anthocyanin absorption is influenced by their chemical structure.

The bioavailability of polyphenol metabolites will vary between individuals and is dependent on complex absorption, distribution, metabolism and excretion ADME mechanisms involving phase I and II metabolism of phenolic molecules [ 76 ].

Also, a systematic review has shown that the intake of fruit juice offered similar protection against cognitive decline to the intake of whole fruit [ 77 ] and thus a similar proportion of bioactive phytochemicals must remain in the processed products. Unfortunately, the current meta-analyses did not sufficiently support a role for fruits or other fruit forms to improve cognition and mood.

Although our meta-analysis lacks evidence to support improvements in mood by specific fruit interventions, another meta-analysis with 10 observational studies involving , participants suggested an inverse association of fruit RR 0.

A previous systematic review has also assessed the association between cognitive benefits and fruit consumption but only included limited evidence from juice interventions, where improvements to memory in mildly cognitive-impaired adults after 12—16 weeks of consumption were illustrated [ 12 ].

The high levels of flavonoid metabolites e. anthocyanidin from flavonoid-rich fruit can transport through blood brain barrier into regions such as the hippocampus to impact on memory and learning [ 79 ]. The poly phenol metabolites attenuated neuro-inflammatory processes via regulation of nuclear factor NF -κB translocation into the nucleus and modulation of IκBα levels by crossing the blood brain barrier endothelium and exerting beneficial effects in different neuronal systems e.

cell lines, primary cultures and in vitro three-dimensional human cell model [ 80 ]. Currently, the majority of evidence in this area has included the association between intake of fruit combined with vegetable intake and cognitive function.

Although insufficient data were entered for meta-analysis for each fruit subgroup, blueberry and grape powders providing Long-term investigations assessing the impact of whole blueberry intervention on cognition are also scarce and worth exploring, given that a large effect size was reported [ 47 ].

Thirteen out of 16 total RCTs in this review recruited older participants and only one study recruited young adults 18 years old athletes without any improvements to cognition or mood shown. Only one intervention examined the effect of long-term supplementation with whole frozen fruit on cognition in this review, no fresh fruit was identified in the previous interventions, which could be due to the difficulty of storage and allocation during the intervention.

Fresh whole fruit is generally how the fruit is consumed, which highlights a novel and necessary intervention in future studies. Increased dietary fructose following sucrose intake is reported to increase de novo lipogenesis and very-low-density lipoprotein levels, which has been shown to increase the risk of developing non-alcoholic fatty liver disease [ 84 ].

Therefore, any health promotion effects of increasing fruit intake by juice consumption should be made with caution. Validation of metabolites and biomarkers for cognitive impairment should be incorporated into future trials to help identify the potential mechanisms underlying any influence between fruit-based intake and cognitive health.

To our knowledge, this is the first systematic review and meta-analysis to compare the impact of various forms of specific fruits in isolation from other food supplementation on cognition. Firstly, in addition to the comprehensive search of the literature in the topic, we also applied the newly developed Hartung-Knapp-Sidik-Jonkman method for modelling random effects in meta-analysis.

Secondly, the interventions included in this review have assessed either general cognitive performance or specific cognitive domains using well-established cognitive tasks. There are limitations to our review. Although our systematic review showed positive results in interventions supplementing with blueberry or grape, the small sample size and moderate to high risks of bias for studies quality that used the same cognitive task in the searched literature may partially explain the lack of support from our meta-analysis.

It also should be noted that generally the cognitive tasks chosen in each intervention study are not uniform because of the polyfactorial nature of neurocognitive measures [ 85 ]. In the current review, not all the domain-specific tasks data could be entered into meta-analyses assessing the effect of the same type of fruit interventions on the specific cognitive domain, thus the effect size derived from the meta-analyses was inevitably under-estimated.

A crossover design is the most appropriate design when comparing a nutritional intervention against placebo since all participants serve as their own control and only three studies applied a crossover design [ 43 , 57 , 58 ]. Only one citrus intervention RCT supplementing orange juice was included, which led to limited exploration of the effect of citrus fruit intervention on cognition [ 43 ].

Due to the small number of studies in each pooled analysis, we were also unable to evaluate whether the effects can be influenced by participant characteristics e. physical activity, sex or to explore the high heterogeneity by subgroup analysis.

To our knowledge, this is the first review of the impact on cognitive health following consumption of different varieties of fruit and different processed forms such as freeze-dried powdered fruit or fruit juice. Apart from fruit juice, promising results were also demonstrated among limited studies supplementing whole frozen or powdered forms of fruit grape powder, frozen and powdered blueberries.

The data that support the findings of this study are available from the corresponding author, JL, upon reasonable request. Deary IJ, Corley J, Gow AJ, Harris SE, Houlihan LM, Marioni RE, et al.

Age-associated cognitive decline. Br Med Bull. Article Google Scholar. Clionsky M, Clionsky E. Dementia screening: saying no to the USPSTF and yes to brief cognitive evaluation. J Alzheimers Dis Parkinsonism.

Workman B, Dickson F, Green S. Early dementia: optimal management in general practice. Aust Fam Physician. Google Scholar. The study showed that treating with hesperidin decreased SIH after rt-PA treatment and improved the recovery of participants with acute brain ischemic stroke within one day of rt-PA.

Researchers conducted another clinical trial with 75 participants between 40 to 65 years who had experienced a heart attack. Daily hesperidin supplementation for four weeks decreased inflammatory markers. It also increased adiponectin a signaling molecule regulating sugar and fat metabolism and high-density lipoprotein cholesterol.

Researchers concluded that certain flavonoids in the diet are associated with heart health benefits. Most participants were people assigned male at birth, so the findings may not be applied to the general population. In a study, researchers conducted a clinical trial of individuals aged between 18 and 75 with acute hemorrhoidal disease.

A mixture of flavonoids consisting of diosmin, troxerutin, and hesperidin for 12 days reduced anal pain and bleeding compared to a placebo a treatment without any medicinal value.

Additionally, the group treated with the mixture of flavonoids experienced a more rapid, steady improvement in swelling and blood clots compared to the placebo group. After six days, the amount of oral pain medication needed by those taking the bioflavonoids was also lower. As hesperidin was combined with diosmin and troxerutin, the effect of hesperidin alone on acute hemorrhoidal disease remains unclear.

Because hesperidin was combined with diosmin to manage venous ulcers, it is unclear if hesperidin alone positively affects venous ulcers.

In a study published in , researchers conducted a clinical trial in 64 individuals aged between 30 and 65 years with a history of diabetes for at least three years. Hesperidin use for six weeks improved antioxidant capacity and blood sugar control and reduced oxidative DNA damage and lipid peroxidation in people with type 2 diabetes.

Further study with larger sample size is warranted to confirm the results. Another clinical trial was conducted with 50 participants between 18 and 70 years old with metabolic dysfunction-associated steatotic liver disease MASLD, formerly known as nonalcoholic fatty liver disease or NAFLD.

One gram of hesperidin for 12 weeks, accompanied by diet and physical activity, improved MASLD compared to a placebo. It lowered inflammatory markers and improved lipid profiles. Similarly, another clinical trial performed on participants with MASLD found that hesperidin and flaxseed supplementation, alone or in combination, for 12 weeks improved sugar and fat metabolism and reduced inflammatory markers.

The study was limited due to its design and potential for bias. Hesperidin alleviated diabetic neuropathy and oxidative stress, according to a rat study cited in a systematic review. More clinical trials in humans are needed to clarify the efficacy of hesperidin in alleviating diabetic neuropathy.

In a test tube in vitro model of retinal ganglial cells bridging eye nerve cells , hesperidin protected against high glucose -induced cell death. Furthermore, a study in rat models found that hesperidin decreased blood sugar levels and pro-inflammatory cytokines inflammatory markers.

Nevertheless, human clinical trials are needed to verify the efficacy of citrus flavonoids, such as hesperidin, in humans. A clinical study in 44 healthy young adults between age 18 and 30 showed increased blood flow to the brain two hours after drinking mL of citrus juice containing a little over 42 mg of hesperidin.

More human clinical studies with larger sample sizes are needed to understand how hesperidin enhances cognitive function.

In a clinical trial of 37 healthy older adults between 60 and 81 years old, daily flavanone-rich orange juice containing hesperidin and narirutin showed beneficial effects on cognitive function.

Furthermore, the group that consumed orange juice with higher hesperidin content had better cognitive, executive, and memory function than those with a lower amount of hesperidin. Since this study was in healthy older adults, further research could investigate the potential for hesperidin to reduce cognitive decline in older adults or those with neurodegenerative disease.

However, human clinical studies are needed to clarify hesperidin's effects in protecting and enhancing brain function for these particular conditions. Your healthcare provider may recommend you take hesperidin for specific reasons.

However, consuming a supplement like hesperidin may have potential side effects. These side effects may be common or severe. Some hesperidin products list the following as some of the potential side effects:.

No side effects were reported in clinical studies assessing the efficacy of hesperidin supplementation on high blood pressure, hemorrhoidal disease, type 2 diabetes, and MASLD. In ischemic stroke, hesperidin has been shown to improve the adverse effects of rt-PA therapy.

In an animal study of male and female rats with high blood pressure, hesperidin increased urinary volume and sodium elimination but did not cause any change in potassium excretion. In short, hesperidin acted somewhat like a diuretic , or water pill.

However, these same effects may not occur in humans. High-quality studies using hesperidin would need to be done with human subjects before conclusions can be made on fluid- and sodium-excretion effects of hesperidin. No serious adverse effects were reported in a study evaluating the effect of hesperidin supplementation for heart attack.

In general, hesperidin is well-tolerated and safe. However, the following conditions were excluded in clinical trials looking into the therapeutic effect of hesperidin:. Avoid using hesperidin if you have a known allergy or intolerance to flavonoids or citrus products.

Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs. The following doses of hesperidin were used in clinical trials for various conditions:.

Based on clinical trials, no more than mg of hesperidin daily was safe for humans. However, a daily hesperidin dose of 1 gram equivalent to 1, mg has been used in MASLD. Even though this dose is more than the daily hesperidin dose of mg from other clinical trials, no side effects were reported.

The safety of long-term use of any of these amounts remains unclear. Hesperidin may interact with the following medications:. It is essential to carefully read a supplement's ingredients list and nutrition facts panel to learn which ingredients and how much of each ingredient is included.

Please review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications.

Store hesperidin in a cool, dry place. Keep hesperidin away from direct sunlight. Discard as indicated on the packaging. Keep it out of the reach of children and pets. The flavonoids listed above are similar to hesperidin in that they are citrus-derived.

Hesperidin, naringenin, eriodictyol, naringin, narirutin, poncirin, didymin, and prunin belong to the flavanone subclass of flavonoids. Apigenin, diosmetin, luteolin, rhoifolin, and diosmin belong to the flavone subclass, while nobiletin and tangeretin belong to the polymethoxyflavone subclass.

Quercetin, kaempferol, and rutin belong to the flavonol subclass. Depending on the uses, hesperidin can be combined with other flavonoids. For example, diosmin and hesperidin are used together to manage chronic venous disease.

Structurally, hesperidin is a flavanone glycoside composed of hesperetin the aglycone form or nonsugar part of hesperidin and the disaccharide rutinose the sugar part.

Hesperetin is generally considered active after removing the sugar part of hesperidin. Another difference is that whereas hesperidin is absorbed in the large intestine, hesperetin is mainly absorbed in the small intestine.

Citrus fruits contain hesperidin, such as lemons, limes, mandarins, oranges, and grapefruits. However, the absorption and metabolism of hesperidin vary depending on the preparation of the citrus fruit.

For example, the availability of hesperidin from orange juice has been shown to be greater than that of whole oranges. Citrinin, a mixture of two flavonoids, eriodictyol, and hesperidin, was observed to possess a vitamin-like activity.

Hence, bioflavonoids e. Hesperidin can be obtained via food or supplements. However, the poor absorption of hesperidin has led to an interest in developing hesperidin supplement formulations with enhanced absorption.

Citrus fruits that are a source of hesperidin include the following:. Like other bioflavonoids, hesperidin works best when given with vitamin C. Hesperidin from orange juice has greater availability compared to hesperidin from whole oranges. Moreover, hesperidin levels have been shown to be 3 times greater in commercially squeezed orange juice than in home-squeezed orange juice.

Citrus fruits, especially grapefruit juice , interact with certain medications. Please consult with your healthcare provider before adding them to your diet. Additionally, reading the nutrition fact label is essential as some juices may contain high amounts of sugar.

Hesperidin is available as capsules and powders. It is also used in tablet form with other flavonoids, such as diosmin. The absorption of hesperidin relies on the conversion of hesperidin to hesperetin the more readily absorbed form by bacteria in the colon.

As hesperidin is composed of hesperetin the non-sugar part and rutinose the sugar part , removing hesperidin's sugar to form hesperetin improves absorption. The dependence of intestinal microbiota to convert hesperidin the food-bound form to hesperetin the active form of hesperidin suggests that the difference in gut microbiota between individuals contributes to variability in the absorption and metabolism of hesperidin.

The micronized 2S hesperidin form, found naturally in orange juice, has the highest rate and extent of absorption.

Few strategies have been developed to improve the bioavailability how well something is absorbed of hesperidin and hesperetin.

One of the strategies involved loading hesperidin onto agents known as metallic nanoparticles and assessing it in breast cancer lab models. It was found that this formulation delivered hesperidin to tumor cells more effectively. Another strategy involved offering hesperetin and other flavonoids, such as quercetin, to improve hesperetin absorption in breast cancer patients.

Mixing hesperidin with chitoolIgosaccharide the degraded product of chitin, a major part of crab, lobster, and shrimp shells enhanced hesperidin's water solubility for greater absorption and antioxidant effects.

Furthermore, the methylated form of hesperidin, also known as hesperidin methyl chalcone , is highly water soluble. Hesperidin, a flavonoid within the flavanone subclass, is derived from citrus fruits and has antioxidant and anti-inflammatory properties.

Human and lab studies have demonstrated the therapeutic potential of hesperidin in heart disease, blood vessel disorders, metabolic disorders, and neurodegenerative diseases.

No significant side effects have been reported in clinical studies. However, caution should be taken if you have a history of bleeding or blood-clotting disorders and if you take certain medications, such as blood thinners, blood pressure-lowering drugs, including calcium channel blockers, and certain anticancer drugs.

It is also important to note that while citrus fruits are a source of hesperidin, they can interact with certain medications.

Speak with your healthcare provider to discuss whether citrus fruits are appropriate for you. Dementia data taken from a long-term care database showed benefits of increased citrus consumption. Facebook Twitter LinkedIn.

Kim Hayes,. Published July 11, Join AARP. MEMBERS ONLY. Learn More. HOT DEALS SAVE MONEY WITH THESE LIMITED-TIME OFFERS.