Health benefits of strawberry and recent scientific studies on anthocyanins and flavonoids.

1. FRUIT AS MEDICINE:
STRAWBERRY,
FRAGARIA ANANASSA
By
Kevin KF Ng, MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL, USA
Email: kevinng68@gmail.com
A Slide Presentation for HealthCare Professionals. Jan 2021

2. Lecture outline
▪ What is a strawberry?
▪ History
▪ Global production & consumption
▪ Scientific classification
▪ Scientific publications
▪ Nutrients and phytochemicals
▪ Animal and human studies
▪ Side effects and toxicity
▪ Summary

3. What is a strawberry?
▪ A strawberry is a short plant in the wild strawberry genus of the rose family.
▪ The name is also used for its very common sweet edible "fruit" and for
flavors that taste like it.
▪ The real fruit of the plant are the tiny "seeds" around the "fruit", which is
actually a sweet swelling of the plant's stem around the fruit,
▪ The plant grown today is a mix of two other species of wild strawberries and
was first grown in the 1750s.
seeds
fruit

4. HISTORY

5. A Brief History of the Strawberry Plant
Adapted from https://strawberryplants.org/strawberry-plant/

6. GLOBAL PRODUCTION & CONSUMPTION

7. China is the World's leading Strawberry producer with
3,801,865 tonnes yearly production. (2020)
https://www.atlasbig.com/en-us/countries-strawberry-production

8. China increased its strawberry consumption (2018)
▪ The countries with the highest consumption were:
1. China (41%),
2. the U.S. (16%),
3. Egypt (5%),
4. Turkey (4%),
5. Mexico (4%) and
6. Germany (3%),
▪ together comprising almost 73% of global consumption.
https://www.freshfruitportal.com/news/2018/06/04/global-strawberry-market-continues-to-expand-report-
finds/#:~:text=China%20increased%20its%20strawberry%20consumption,almost%2073%25%20of%20global%20co
nsumption.

9. Top 10 Fruits Sold in the U.S. in 2019
https://www.pma.com/content/articles/top-20-fruits-and-vegetables-sold-in-the-us

10. SCIENTIFIC CLASSIFICATION

11. According to the Germplasm Resources Information Network
(part of the United States Department of Agriculture),
there are 103 distinct species and subspecies of strawberry plants. (Oct 31, 2019)

12. Varieties of Strawberry
https://luv2garden.com/strawberry_varieties.html

13. ANATOMY

14. Anatomy of a strawberry
https://www.pinterest.com/pin/515380751086962061/
seed

15. SCIENTIFIC STUDIES

16. Number of articles “strawberries” in PubMed from
1884 to 2020
https://pubmed.ncbi.nlm.nih.gov/?term=Strawberries
Total 5,923

17. NUTRIENTS AND
PHYTOCHEMICALS

18. Outline of Nutrients and phytochemicals in strawberry

19. Nutrient composition of raw strawberry (per 100 g)
Macronutrients
Water 90.95 g
Energy 32 kcal
Protein 0.67 g
Total lipid (fat) 0.3 g
Carbohydrate, by difference 7.68 g
Fiber, total dietary 2 g
Sugars, total including NLEA 4.89 g
Micronutrients
Minerals
Calcium, Ca 16 mg
Iron, Fe 0.41 mg
Magnesium, Mg 13 g
Phosphorus, P 24 mg
Potassium, K 153 mg
Sodium, Na 1 g
Zinc, Zn 0.14 mg
Copper, Cu 0.048 mg
Selenium, Se 0.4 µg
Micronutrients
Vitamins
Vitamin C, total ascorbic acid 58.8 mg
Thiamin 0.024 mg
Riboflavin 0.022 mg
Niacin 0.386 mg
Vitamin B-6 0.047 mg
Folate, total 24 µg
Folate, food 24 µg
Folate, DFE 24 µg
Choline, total 5.7 mg
Vitamin A, RAE 1 µg
Carotene, beta 7 µg
Lutein + zeaxanthin 26 µg
Vitamin E (alpha-tocopherol) 0.29 mg
Vitamin K (phylloquinone) 2.2 µg
https://fdc.nal.usda.gov/fdc-app.html#/food-details/1102710/nutrients

20. Major phytochemicals in strawberries (Fragaria genus) 2020
Adapted from https://www.mdpi.com/1420-3049/25/3/498/htm

21. Chemical composition of strawberry and blueberry
Nutrients 2019, 11, 1510

22. Structure of anthocyanins.
(A) The structural classification of the six most common anthocyanins;
(B) The structural classification of the four most common anthocyanins
identified in strawberry and black raspberry (2019)
https://www.researchgate.net/publication/333597443_Chemopreventive_Effects_of_Stra
wberry_and_Black_Raspberry_on_Colorectal_Cancer_in_Inflammatory_Bowel_Disease

23. PHARMACOKINETICS

24. Determinant factors of the oral bioavailability of
bioactive anthocyanins
Modified from https://www.hindawi.com/journals/jo/2017/7351976/fig1/

25. Pharmacokinetics of anthocyanins in humans
after oral dose of 68-1,300 mg
‫٭‬https://www.sciencedirect.com/science/article/abs/pii/S1756464613001370
‫٭‬

26. Bioavailability study with radio-labelled anthocyanin
in humans (2019)
▪ After ingestion, anthocyanins are converted to a large number of products via
chemical events, human and microbial metabolism.
▪ Within 6 h after humans ingested 13C-labeled anthocyanin, substantial 13C-labeled
CO2 was detected in exhaled breath, which demonstrated rapid and complete
anthocyanin catabolism.
▪ >50% of the 13C still remained in the body after 48 h .
▪ Anthocyanins and their phase 2 metabolites persist in urine long after anthocyanin
intake , probably due to their transport in bile .
▪ Due to the catabolic action of gastrointestinal microflora on anthocyanins and other
food polyphenolics, phenolic acid products are very abundant in the large intestine .
https://academic.oup.com/advances/advance-article/doi/10.1093/advances/nmz065/5536953

27. BIOLOGICAL ACTIVITIES

28. Main biological activities reported in the literature (2020):
in vitro and in vivo studies of strawberries
▪ Main activities:
▪ Antioxidant Properties
▪ Anti-Inflammatory Properties
▪ Other activities:
▪ Anti-microbial
▪ Anti-allergenic
▪ Anti-diabetic
▪ Antihyperuricemic
▪ Anti-obesity
▪ Hepatoprotective
▪ Anticancer
▪ Cytotoxic
▪ Antineoplastic
▪ Chemopreventive
▪ Skin-lightening
https://www.mdpi.com/1420-3049/25/3/498/htm

29. Cyclooxygenase inhibitory and antioxidant cyanidin glycosides
in cherries and berries (2001)
▪ Anthocyanins from tart cherries, Prunus cerasus L. (Rosaceae) cv. Balaton and Montmorency; sweet
cherries, Prunus avium L. (Rosaceae); bilberries, Vaccinum myrtillus L. (Ericaceae); blackberries, Rubus
sp. (Rosaceae); blueberries var. Jersey, Vaccinium corymbosum L. (Ericaceae); cranberries var. Early
Black, Vaccinium macrocarpon Ait. (Ericaceae); elderberries, Sambucus canadensis (Caprifoliaceae);
raspberries, Rubus idaeus (Rosaceae); and strawberries var. Honeoye, Fragaria x ananassa Duch.
(Rosaceae), were investigated for cyclooxygenase inhibitory and antioxidant activities.
▪ The presence and levels of cyanidin-3-glucosylrutinoside 1 and cyanidin-3-rutinoside 2 were determined
in the fruits using HPLC. The antioxidant activity of anthocyanins from cherries was comparable to the
commercial antioxidants, tert-butylhydroquinone, butylated hydroxytoluene and butylated
hydroxyanisole, and superior to vitamin E, at a test concentration of 125 microg/ml.
▪ Anthocyanins from raspberries and sweet cherries demonstrated 45% and 47% cyclooxygenase-I and
cyclooxygenase-II inhibitory activities, respectively, when assayed at 125 microg/ml. The cyclooxygenase
inhibitory activities of anthocyanins from these fruits were comparable to those of ibuprofen and
naproxen at 10 microM concentrations. Anthocyanins 1 and 2 are present in both cherries and raspberry.
The yields of pure anthocyanins 1 and 2 in 100 g Balaton and Montmorency tart cherries, sweet cherries
and raspberries were 21, 16.5; 11, 5; 4.95, 21; and 4.65, 13.5 mg, respectively.
▪ Fresh blackberries and strawberries contained only anthocyanin 2 in yields of 24 and 22.5 mg/100 g,
respectively. Anthocyanins 1 and 2 were not found in bilberries, blueberries, cranberries or elderberries.
https://www.researchgate.net/publication/11658298_Cyclooxygenase_inhibitory_and_antioxidant_cyanidin_glycosides_in_cherries_and_berries

30. Anti-inflammatory and wound healing properties of polyphenolic
extracts from strawberry and blackberry fruits (2019)
▪ The polyphenolic profiles by HPLC-TOF-MS of strawberry 'San Andreas' and blackberry 'Black Satin' crude extracts (CE) were analyzed.
▪ Anthocyanin-enriched fractions (AEFs) and proanthocyanidin-enriched fractions (PEFs) were prepared, and all samples were probed for
in vitro anti-inflammatory and wound healing effects in a LPS-stimulated RAW 264.7 macrophage model and in a skin fibroblast
migration and proliferation assay, respectively.
▪ Blackberry samples exhibited higher ROS reduction than strawberry's (up to 50% ROS suppression). Berries CEs exhibited 20%
inhibition in Cox-2 gene expression, while AEFs and PEFs were inactive at the same concentration.
▪ Strawberry AEF and PEF were more active against IL-1β and IL-6 gene expressions than the similar fractions from blackberry, where PEF
was more active than AEF (75% suppression by strawberry PEF).
▪ Moreover, berry PEFs were the active polyphenol fraction against iNOS gene expression (50% and 65% gen suppression by strawberry
and blackberry PEF, respectively), mirroring results of NO synthesis suppression. The cell migration potential of berry polyphenolics
was associated with anthocyanins.
▪ AEFs showed fibroblast migration around 50% of that registered for the positive control.
▪ Results obtained in this work highlight the anti-inflammatory properties of berry polyphenolics, especially due to proanthocyanidins.
Moreover, promising results were obtained about the effects of berry anthocyanins on wound healing.
▪ Keywords: Anthocyanins; Cyclooxygenase-2; Fragaria ananassa; Interleukin-6; Proanthocyanidins; Rubus fruticosus; Skin cell migration.
https://pubmed.ncbi.nlm.nih.gov/31108769/

31. Polyphenol-Rich Strawberry Extract Protects HuDe
(Human dermal fibroblasts) cells and prevented DNA damage (2014)
https://www.mdpi.com/1420-3049/19/6/7798/htm
T.I.=intensity of fluorescence

32. Antineoplastic activity of strawberry (Fragaria × ananassa
Duch.) crude extracts on B16-F10 melanoma cells (2014)
https://pubs.rsc.org/en/content/articlelanding/2014/mb/c3mb70316a/unauth#!divAbstract

33. CLINICAL STUDIES

34. Medicinal Uses of Strawberry Plants (march 19, 2020)
Dr. Duke’s Phytochemical and Ethnobotanical Databases.
721 medical uses
https://strawberryplants.org/medicinal-uses-of-strawberry-plants/

35. Clinical studies of strawberries in humans
▪ Cardiovascular risk factors
▪ Pain and inflammation
▪ Insulin in Obese patients
▪ Hyperglycemia
▪ Hyperlipidemia
▪ Hypertension
▪ Skin disorders

36. Freeze dried strawberry powder improved vascular function (2019)
https://pubs.rsc.org/en/content/getauthorversionpdf/C9FO01844A

37. Effect of acute consumption of strawberry jam on glycaemic status in
(A)non-complicated and (B)type 2 diabetic obese volunteers:
A pilot study (2011)
control strawberry jam (CSJ, open circle)
https://www.researchgate.net/figure/a-Incremental-glucose-concentration-mmol-l-before-and-after-the-ingestion-of-the_fig1_257780213
experimental strawberry jam (ESJ, filled circle)
normal volunteers type 2 diabetic obese volunteers

38. Postprandial insulin concentrations in abdominally obese individuals with insulin resistance:
dose-response effect of strawberry containing beverages (10, 20, and 40 g FDS) versus control beverage (0 g FDS) when
consumed with high-carbohydrate, high-fat meal, n = 21 (2016)
https://www.researchgate.net/figure/Postprandial-insulin-concentrations-in-abdominally-obese-individuals-with-insulin_fig4_292990453
FDS=freeze-dried strawberries

39. The effect of strawberries in a cholesterol-lowering
dietary portfolio (2008)
https://www.metabolismjournal.com/article/S0026-0495(08)00269-2/pdf
LDL-cholesterol
%compliance
strawberry supplementation reduced oxidative damage to LDL

40. Summary of effects of strawberry supplementation on
cardiovascular risk factors:
a comprehensive systematic review and meta-analysis of randomized controlled trials (2019)
▪ Strawberry supplementation decreased
▪ circulating oxidized LDL (MD = −5.8 ng ml−1, p = 0.012),
▪ malondialdehyde (0.309 μmol L−1, p = 0.002),
▪ C-reactive protein (MD = −0.472 mg L−1, p = 0.003),
▪ total cholesterol (MD = −6.49 mg dL−1, p = 0.019),
▪ diastolic blood pressure (MD = −2.220 mmHg, p = 0.033).
▪ It raised fasting blood sugar (MD = 2.083 mg dl−1; p = 0.040)
https://pubs.rsc.org/en/content/articlelanding/2019/fo/c9fo01684h/unauth#!divAbstract
MD=mean difference
ATHEROMA

41. Effects of strawberry intervention on cardiovascular risk factors:
a meta-analysis of randomised controlled trials (2020)
https://pubmed.ncbi.nlm.nih.gov/32238201/

42. Strawberries Improve Pain and Inflammation in Obese Adults
with Radiographic Evidence of Knee Osteoarthritis (2017)
▪ Osteoarthritis (OA), the most common form of arthritis, is a significant public health burden in U.S. adults. Among its many risk
factors, obesity is a key player, causing inflammation, pain, impaired joint function, and reduced quality of life. Dietary
polyphenols and other bioactive compounds in berries, curcumin, and tea have shown effects in ameliorating pain and
inflammation in OA, but few clinical studies have been reported.
▪ The purpose of the present study was to examine the effects of dietary strawberries on pain, markers of inflammation, and quality
of life indicators in obese adults with OA of the knee. In a randomized, double-blind cross-over trial, adults with radiographic
evidence of knee OA (n = 17; body mass index (BMI): (mean ± SD) 39.1 ± 1.5; age (years): 57 ± 7) were randomized to a
reconstituted freeze-dried strawberry beverage (50 g/day) or control beverage daily, each for 12 weeks, separated by a 2-week
washout phase (total duration, 26 weeks).
▪ Blood draws and assessments of pain and quality of life indicators were conducted using the Visual Analog Scale for Pain (VAS
Pain), Measures of Intermittent and Constant Osteoarthritis Pain (ICOAP), and Health Assessment Questionnaire-Disability Index
(HAQ-DI) questionnaires, which were completed at baseline and at weeks 12, 14, and 26 of the study.
▪ Among the serum biomarkers of inflammation and cartilage degradation, interleukin (IL)-6, IL-1β, and matrix metalloproteinase
(MMP)-3 were significantly decreased after strawberry vs. control treatment (all p < 0.05). Strawberry supplementation also
significantly reduced constant, intermittent, and total pain as evaluated by the ICOAP questionnaire as well as the HAQ-DI scores
(all p < 0.05).
▪ No effects of treatment were noted on serum C-reactive protein (CRP), nitrite, glucose, and lipid profiles. Dietary strawberries may
have significant analgesic and anti-inflammatory effects in obese adults with established knee OA.
▪ Keywords: inflammation; knee osteoarthritis; pain; strawberries.
https://pubmed.ncbi.nlm.nih.gov/28846633/

43. Strawberries decrease circulating levels of tumor necrosis factor
and lipid peroxides in knee osteoarthritis in obese adults (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310224/

44. Effects of dietary strawberry powder on blood lipids and
inflammatory markers in obese human subjects (2012)
▪ Obesity is a strong risk factor for the development of CVD, hypertension and type 2 diabetes. The overall goal of the
present pilot study was to feed strawberries, in the form of freeze-dried powder, to obese subjects to determine whether
dietary strawberries beneficially altered lipid profiles and reduced blood markers of inflammation compared with a
control intervention.
▪ A total of twenty healthy subjects (thirteen females and seven males) aged between 20 and 50 years with a BMI between
30 and 40 kg/m2 completed the present 7-week double-blind, randomised, cross-over trial.
▪ Each subject received a prepared diet 7 d/week for 7 weeks consisting of approximately 35 % of energy from fat, 20 %
protein, 45 % carbohydrate and 14 g fibre. Blood was collected on days 1 and 8 for baseline information.
▪ After the first week, subjects were randomly assigned to the strawberry powder (equivalent to four servings of frozen
strawberries) or control (strawberry-flavoured) intervention for 3 weeks. For the remaining 3 weeks, subjects crossed
over to the opposite intervention.
▪ Blood was collected again at the end of weeks 3, 4, 6 and 7. A comprehensive chemistry panel, lipid profile analyses
and measurement of inflammatory mediators were performed for each blood draw. A 3-week dietary intervention with
strawberry powder reduced plasma concentrations of cholesterol and small HDL-cholesterol particles, and increased
LDL particle size in obese subjects (P < 0·05).
▪ Dietary strawberry powder reduced risk factors for CVD, stroke and diabetes in obese volunteers, suggesting a potential
role for strawberries as a dietary means to decrease obesity-related disease.
https://www.researchgate.net/publication/51783960_Effects_of_dietary_strawberry_
powder_on_blood_lipids_and_inflammatory_markers_in_obese_human_subjects

45. Effects of Dietary Strawberry Supplementation on Antioxidant
Biomarkers in Obese Adults with Above Optimal Serum Lipids 2016
▪ Berries have shown several cardiovascular health benefits and have been associated with
antioxidant functions in experimental models. Clinical studies are limited. We examined the
antioxidant effects of freeze-dried strawberries (FDS) in adults [; age: years;
BMI: kg/m2 (mean ± SD)] with abdominal adiposity and elevated serum lipids. Participants
were randomized to one of the following arms: low dose strawberry (25 g/day FDS), low dose
control beverage (LD-C), high dose strawberry (50 g/d FDS), and high dose control beverage
(HD-C) for 12 weeks. Control beverages were matched for calories and total fiber. Plasma
antioxidant capacity, trace elements (copper, iron, selenium, and zinc), whole blood
glutathione (GSH), and enzyme activity (catalase, glutathione peroxidase, and glutathione
reductase) were examined at screening (0 week) and after 12 weeks’ intervention.
▪ At 12 weeks, plasma antioxidant capacity and glutathione levels were higher in the strawberry
versus control groups (low and high dose FDS: 45% and 42% for plasma antioxidant capacity
and 28% and 36% for glutathione, resp.); glutathione was higher in the high versus low dose
strawberry group (all ). Serum catalase activity was higher in the low dose strawberry (43%)
versus control group (). No differences were noted in plasma trace elements and glutathione
enzyme activity. Dietary strawberries may selectively increase plasma antioxidant biomarkers
in obese adults with elevated lipids.
https://www.hindawi.com/journals/jnme/2016/391063
0/

46. SIDE EFFECTS & ALLERGY

47. The Potential Side Effects of Eating Too Many Strawberries
https://www.everydayhealth.com/diet-nutrition/diet/strawberries-nutrition-facts-health-benefits-recipes-more/

48. Allergy
▪ Some people experience an anaphylactoid reaction to
eating strawberries.
▪ The most common form of this reaction is oral allergy
syndrome, but symptoms may also mimic hay fever or
include dermatitis or hives, and, in severe cases, may cause
breathing problems
▪ Proteomic studies indicate that the allergen may be tied to a
protein named Fra a1 (Fragaria allergen1).
▪ White-fruited strawberry cultivars, lacking Fra a1, may be an
option for strawberry allergy sufferers.
https://www.pinterest.com/pin/367887863284275001/

49. COMMERCIAL PRODUCTS

50. Strawberry drinks, puddings and cakes

51. SUMMARY

52. Summary
▪ Strawberry is a fruit derived from the plant that belongs to the rose family .
▪ It is rich in vitamins, minerals and phytochemicals.
▪ The phytochemicals (phenolic acids, flavonoids and ellagitannins) have
been shown to be beneficial for health.
▪ Strawberry is now considered to be a “superfood”

53. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
53