Reading Time: 13 minutes

 

Improve your brain with food

Your brain is a seed of your thoughts, behavior, and emotions. If you want to work efficiently, keep up happy mood and recover well during the night, you need to provide the brain input which helps it to produce all necessary signaling hormones (neurotransmitters), energy, and new neurons. The brain also needs help in removing toxins and waste products from the cells. You have the power to improve these processes by because they largely depend on your diet.

 

Foods have been widely studied in the context of brain function. With eating right, you can:

 

  • Increase energy production in the frontal areas of the brain. For example, The Ketogenic Diet is shown to increase energy production in the Prefrontal Cortex – a brain area important for working memory. (S)

 

  • Provide the brain building blocks for neurotransmitters. For example, eating foods high in folate has been shown to reduce depressive symptoms in depressed patients. Folate belongs to the class of vitamin Bs and acts as a building block for dopamine and serotonin – both of which are important to maintaining optimal mood, motivation, and energy. (S)

 

  • Promote brain cell growth (neurogenesis) and enhance neuroplasticity. For example, in one study researchers studied mice with brain damage and deficient folate metabolism. Researchers enriched the diet of the mice with vitamin B6, riboflavin, folate, and choline. They noticed that the brains of these mice recovered and grew back faster compared to the group of mice who did not eat extra folate or choline. (S)

 

  • Protect the brain from damage and memory disease. Several foods have shown to protect the brain cells from oxidative stress which can cause for example Alzheimer’s disease. (S) These include dietary fatty acids, dark leafy greens, and berries.

 

“Brain foods” refers to those everyday foods which can improve memory, thinking, executive functions and mood. Though the word “brain foods” is not a scientific term, there are plenty of foods which has scientifically shown to improve brain function when they are frequently consumed.  

 

If you want to improve your brain power, add these 6 foods in your diet.

 

1. Eggs – choline and lutein (S)

 

Eggs (especially the yolks) are rich in choline and lutein.

 

Choline

Choline is an important precursor for the neurotransmitter acetylcholine, which is needed for memory and learning. Higher choline intake is linked to better verbal and visual learning and better memory (S) (S)

Choline participates in building myelin around the brain cells. (S) (SMyelin is a fat layer around a brain cell part called axon which protects the brain cell from damage and allows signals in the brain to travel fast and efficiently (which means faster thinking, faster movement, better memory, and executive functions).

 

Choline is also important for the development of a healthy brain in the fetal age, infancy and through childhood. (S)(S) Choline participates to stem cell proliferation and apoptosis and supports the development of a healthy brain structure and function of the child. (S)

 

Lutein

The yellow pigment in the yolk is a xanthophyll carotenoid called lutein. Interestingly, the human body can use lutein from eggs more efficiently than the lutein in the lutein ester supplements or green leafy vegetables. (S)

The levels of neural lutein are associated with Improved brainpower in the areas of visuospatial processing, decision-making, and motor coordination during a cognitive task. (S)

In addition, plasma lutein concentrations are associated with a decreased risk of all-cause dementia and Alzheimer’s Disease. (S)

 

Choosing the best eggs and how to cook them properly

 

  • Eat cage-free organic or “nutraceutical” eggs (enriched with omega-3) – they have been more vitamins and better fatty acid balance than cage-raised eggs (S) (S)

 

  • Choose eggs with a vivid yellow yolk – That’s a sign that it is richer in the neuroprotective carotene (S)

 

  • When you cook the eggs, leave the yolk raw. Heating it will destroy some of its healthy xanthophylls such as lutein. (S)

 

  • The egg white, on the other hand, should be cooked because it denatures avidin and albumin, which interferes with the absorption of vitamin B complex and iron. Albumin can also cause allergies. (S)

 

 

 

 

 

2. Dark leafy greens – antioxidants, lutein, vitamins

Dark leafy greens contain vitamin B1 (thiamin) and B6 (pyridoxine), which fight against harmful substances called AGEs (Advanced glycation end-products), which can cause nerve cell death and memory diseases. (S) (S) (S) Thus, dark leafy greens naturally protect your brain from oxidative stress and toxins.

Dark leafy greens also contain lutein (part of carotenoids or plant color pigments), which is linked to improved cognition and processing speed (see more in eggs). (S)

Dark leaves are also high in vitamin K (phylloquinone), β-carotene, nitrate, folate, kaempferol, and α-tocopherol. A study published in Neurology in January 2018 found that eating at least one serving (half a cup cooked or one cup raw) of leafy green vegetables every day was associated with a slower decline in brain function. (S)

 

Choose the most vitamin-rich greens

  • Nutrient-dense greens include for example kale, spinach, broccoli, broccoli sprouts, and brussels sprouts
  • Aim for dark color (the darker the better)
  • Eat organic to avoid any added chemicals
  • Eat fresh greens if you can

 

3. Dark and raw chocolate 

Cocoa is high in flavonoids (bioactive plant compounds). Flavonoids are linked to various health benefits through their high antioxidant capacity which protects the cells from oxidative stress and improves cell signaling. (S)

Flavanol-rich cocoa has also shown to increase brain blood flow, oxygen consumption and stimulate nerve cell growth. (S)

Dietary flavonoids and antioxidants found in dark chocolate are linked enhanced memory and slowed mental-decline in old age; in some studies, cocoa is even referred as a nutraceutical (i.e. a food product which shows extra health benefits such as preventing a disease). (S)

Cocoa also contains methylxanthines such as theobromine and caffeine, which can boost alertness, reaction times and psychomotor functions especially in a tired state or after sleep deprivation. (S)

 

Choosing high-quality chocolate in the market

  • Choose chocolate with at least 70% cocoa content (or higher), this assures a low sugar content and high antioxidant content in the product. 
  • Use single-origin, organic chocolate to avoid artificial sweeteners and added chemicals
  • High-quality chocolate is milk-free

 

 

4. Fatty fish, cod liver oil, krill oil (S) – omega 3 fatty acids

Fatty fish such as salmon is high in omega-3 fatty acids (polyunsaturated fatty acid; PUFA). Higher intake of PUFAs and omega-3s is linked to improved memory, executive functioning, mood, and motivation. Deprivation of omega-3s is linked to mental illness (such as depression) and poorer memory and cognition.

PUFAs also stimulate nerve cell growth in brain areas important for memory and learning (e.g. hippocampus) and acts as building blocks for brain cell membranes, so they help protect the cell and speed up brain signaling. (S) (S)

PUFAs are also needed for the healthy function of neurotransmitter systems such as serotonergic (mood, memory, learning), dopaminergic (mood, motor functioning, motivation), noradrenergic (energy, action, attention) neurotransmitter systems. (S)

 

Choosing the fish

  • Find fish which comes from pure waters with low mercury content (mercury is toxic for the brain) (S)
  • Farmed fish contain less mercury, but are sometimes fed with antibiotics; if you use farmed fish make sure it has had an antibiotic-free diet and grown in pure water with plenty of space to move freely (S)
  • Fatty fish contain more PUFAs; good sources are for example mackerel, salmon, cod liver oil, and oysters

 

5. Blueberries – anthocyanin, resveratrol

Blueberries are rich in vitamins, flavonoids, anthocyanin, and other important polyphenols such as resveratrol. These are powerful antioxidants and fights against inflammation and protects the brain from oxidative stress and aging.

The polyphenols in berries lower brain cell aging and improve cognitive function (S)

Anthocyanins, a powerful antioxidant which gives blueberries their blue color, can cross the blood-brain barrier and affect brain areas important for learning and memory (e.g. the hippocampus, striatum, and cortex) (S) (S)

Blueberries also increase the brain growth hormone gene expression in the brain areas which control memory and learning (i.e. hippocampus). They also increase levels of other beneficial proteins linked to brain growth (such as IGF-1 and IGF-1R). In addition, these biological benefits have shown to improve plasticity and help brain cells in the hippocampus live longer. (S) (S) (S)

Beneficial flavonoids and polyphenols from berries can accumulate in the brain following long-term consumption. For example, when blueberries and bilberries are consumed in high amounts during life, it has been shown to be particularly beneficial for cognition. (S)

 

Buying and eating berries

  • Look for berries that are firm, dry, plump and smooth-skinned, with a silvery surface bloom
  • When it is blueberry season, eat fresh, local berries which have more antioxidants (and  taste better!)
  • If it is not blueberry season, you can normally find pre-washed, unsweetened local frozen blueberries in the frozen food section

 

 

 

6. Sprouts & cruciferous vegetables – sulforaphane

Sprouts and cruciferous vegetables contain sulforaphane, a compound which regulates the expression of over 200 genes (nrf2 pathway), many of these genes are linked to neuroprotection, mood, and social behavior. (S)

They also increase energy production and antioxidant glutathione in the hippocampus, which helps to protect the cells in the brain area of memory and learning. (S) (S) In a study, sulforaphane improved spatial memory and short term memory in mice who were at risk for cognitive decline. (S) (S)

Sulforaphane has shown to increase protective mechanisms (autophagy flux) in the human brain, showing neuroprotection (S) and was also shown to decreased neuron loss in mice with Alzheimer’s Disease. (S) This means it can and decrease the number of harmful toxins in the brain and protect it from memory disease. Sulforaphane also activates heat shock proteins which have been shown to provide an additional mechanism to protect from memory diseases such as Alzheimer’s Disease. (S)

In addition, it can lower inflammation which has shown to improve mood and cognition. (S)

 

Getting the most (sulforaphane) out of vegetables (S)

 

  • The best source for sulforaphane in broccoli sprouts which contain up to 100x times more glucoraphanin than mature broccoli
  • Sulforaphane is also found in cruciferous vegetables such as broccoli, cauliflower, kale, bok choy, wasabi and cabbage
  • Studies have used about 9-25 mg dosages of extracted sulforaphane which is found in about 65 g of fresh broccoli sprouts
  • Chew the vegetables well to activate sulforaphane from its inactive form, glucoraphanin
  • For maximal sulforaphane, eat vegetables raw or cook at low temperatures (maximum of 140˚C / 284˚F) (S)
  • Boost the bioavailability of sulforaphane by adding mustard seeds or mustard powder to your meals. They contain myrosinase, which increases the availability of sulforaphane, especially in cooked vegetables. (S)

 

 

 

Summary

These foods can boost mood, productivity, energy, and brain health. They can also protect your brain from memory diseases and help to grow new neurons:

  • Eggs
  • Dark leafy greens
  • Cocoa (e.g. dark chocolate)
  • Fatty fish
  • Blueberries
  • Sprouts

Eat organic, fresh eggs to enhance neuroplasticity and brain development.

Choose dark leafy greens which are rich in vitamin B6s and vitamin K (phylloquinone) to prevent cognitive decline and improve brain function. 

In the fish section, use fish high in omega-3 fatty acids, such as salmon, to help brain cells grow, and ensure your neurotransmitters keeps in a healthy balance.

Eat fresh organic blueberries to help the brain to detox and fight against free radicals.

Add broccoli sprouts to your plate for nfr2 activation and to prevent memory disease.

 

Enjoy your brain-boosting meals!

 

References:

  1. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory: Nutritional Neuroscience: Vol 8, No 2. (n.d.). Retrieved August 4, 2019, from https://www.tandfonline.com/doi/abs/10.1080/10284150500078117
  2. Buchman, A. L., Sohel, M., Brown, M., Jenden, D. J., Ahn, C., Roch, M., & Brawley, T. L. (2001). Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. JPEN. Journal of Parenteral and Enteral Nutrition, 25(1), 30–35. https://doi.org/10.1177/014860710102500130
  3. Carrasco‐Pozo, C., Tan, K. N., & Borges, K. (2015). Sulforaphane is anticonvulsant and improves mitochondrial function. Journal of Neurochemistry, 135(5), 932–942. https://doi.org/10.1111/jnc.13361
  4. Casadesus, G., Shukitt-Hale, B., Stellwagen, H. M., Zhu, X., Lee, H.-G., Smith, M. A., & Joseph, J. A. (2004). Modulation of Hippocampal Plasticity and Cognitive Behavior by Short-term Blueberry Supplementation in Aged Rats. Nutritional Neuroscience, 7(5–6), 309–316. https://doi.org/10.1080/10284150400020482
  5. Chen, J.-H., Lin, X., Bu, C., & Zhang, X. (2018). Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutrition & Metabolism, 15. https://doi.org/10.1186/s12986-018-0306-7
  6. Chung, H.-Y., Rasmussen, H. M., & Johnson, E. J. (2004). Lutein Bioavailability Is Higher from Lutein-Enriched Eggs than from Supplements and Spinach in Men. The Journal of Nutrition, 134(8), 1887–1893. https://doi.org/10.1093/jn/134.8.1887
  7. Eisenhauer, B., Natoli, S., Liew, G., & Flood, V. M. (2017). Lutein and Zeaxanthin—Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection. Nutrients, 9(2). https://doi.org/10.3390/nu9020120
  8. Fava, M., & Mischoulon, D. (2009). Folate in Depression: Efficacy, Safety, Differences in Formulations, and Clinical Issues. The Journal of Clinical Psychiatry, 70(suppl 5), 12–17. https://doi.org/10.4088/JCP.8157su1c.03
  9. Francis, S. T., Head, K., Morris, P. G., & Macdonald, I. A. (2006). The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. Journal of Cardiovascular Pharmacology, 47 Suppl 2, S215-220. https://doi.org/10.1097/00005344-200606001-00018
  10. Gao, J., Xiong, B., Zhang, B., Li, S., Huang, N., Zhan, G., … Luo, A. (2018). Sulforaphane Alleviates Lipopolysaccharide-induced Spatial Learning and Memory Dysfunction in Mice: The Role of BDNF-mTOR Signaling Pathway. Neuroscience, 388, 357–366. https://doi.org/10.1016/j.neuroscience.2018.07.052
  11. Hernandez, A. R., Hernandez, C. M., Campos, K., Truckenbrod, L., Federico, Q., Moon, B., … Burke, S. N. (2018). A Ketogenic Diet Improves Cognition and Has Biochemical Effects in Prefrontal Cortex That Are Dissociable From Hippocampus. Frontiers in Aging Neuroscience, 10. https://doi.org/10.3389/fnagi.2018.00391
  12. Hribar, U., & Ulrih, N. P. (2014). The metabolism of anthocyanins. Current Drug Metabolism, 15(1), 3–13.
  13. IJMS | Free Full-Text | Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions. (n.d.). Retrieved August 4, 2019, from https://www.mdpi.com/1422-0067/15/8/14396
  14. Jadavji, N. M., Emmerson, J. T., MacFarlane, A. J., Willmore, W. G., & Smith, P. D. (2017). B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiology of Disease, 103, 89–100. https://doi.org/10.1016/j.nbd.2017.04.001
  15. Kawakita, E., Hashimoto, M., & Shido, O. (2006). Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience, 139(3), 991–997. https://doi.org/10.1016/j.neuroscience.2006.01.021
  16. https://www.excli.de/vol15/Park_13102016_proof.pdf
  17. Kim, J. K., & Park, S. U. (2016a). Current potential health benefits of sulforaphane. EXCLI Journal; 15:Doc571; ISSN 1611-2156. https://doi.org/10.17179/excli2016-485
  18. Lee, J.-H., Jeong, J.-K., & Park, S.-Y. (2014). Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway. Neuroscience, 278, 31–39. https://doi.org/10.1016/j.neuroscience.2014.07.072
  19. Lee, S., Choi, B.-R., Kim, J., LaFerla, F. M., Park, J. H. Y., Han, J.-S., … Kim, J. (2018). Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-β and Tau in a Mouse Model of Alzheimer’s Disease. Molecular Nutrition & Food Research, 62(12), 1800240. https://doi.org/10.1002/mnfr.201800240
  20. Lordelo, M., Fernandes, E., Bessa, R. J. B., & Alves, S. P. (2017). Quality of eggs from different laying hen production systems, from indigenous breeds and specialty eggs. Poultry Science, 96(5), 1485–1491. https://doi.org/10.3382/ps/pew409
  21. Lundebye, A.-K., Lock, E.-J., Rasinger, J. D., Nøstbakken, O. J., Hannisdal, R., Karlsbakk, E., … Ørnsrud, R. (2017). Lower levels of Persistent Organic Pollutants, metals and the marine omega 3-fatty acid DHA in farmed compared to wild Atlantic salmon (Salmo salar). Environmental Research, 155, 49–59. https://doi.org/10.1016/j.envres.2017.01.026
  22. Mellott, T. J., Follettie, M. T., Diesl, V., Hill, A. A., Lopez-Coviella, I., & Blusztajn, J. K. (2007). Prenatal choline availability modulates hippocampal and cerebral cortical gene expression. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 21(7), 1311–1323. https://doi.org/10.1096/fj.06-6597com
  23. Miranda, J. M., Anton, X., Redondo-Valbuena, C., Roca-Saavedra, P., Rodriguez, J. A., Lamas, A., … Cepeda, A. (2015). Egg and Egg-Derived Foods: Effects on Human Health and Use as Functional Foods. Nutrients, 7(1), 706–729. https://doi.org/10.3390/nu7010706
  24. Modulation of Hippocampal Plasticity and Cognitive Behavior by Short-term Blueberry Supplementation in Aged Rats: Nutritional Neuroscience: Vol 7, No 5-6. (n.d.). Retrieved August 4, 2019, from https://www.tandfonline.com/doi/abs/10.1080/10284150400020482
  25. Morris, M. C. (2009). The role of nutrition in Alzheimer’s disease: epidemiological evidence. European Journal of Neurology, 16(s1), 1–7. https://doi.org/10.1111/j.1468-1331.2009.02735.x
  26. Morris, Martha Clare, Wang, Y., Barnes, L. L., Bennett, D. A., Dawson-Hughes, B., & Booth, S. L. (2018). Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study. Neurology, 90(3), e214–e222. https://doi.org/10.1212/WNL.0000000000004815
  27. Mudd, A. T., Getty, C. M., & Dilger, R. N. (2018). Maternal Dietary Choline Status Influences Brain Gray and White Matter Development in Young Pigs. Current Developments in Nutrition, 2(6). https://doi.org/10.1093/cdn/nzy015
  28. Niculescu, M. D., Yamamuro, Y., & Zeisel, S. H. (2004). Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene. Journal of Neurochemistry, 89(5), 1252–1259. https://doi.org/10.1111/j.1471-4159.2004.02414.x
  29. Nutrients | Free Full-Text | Lutein and Zeaxanthin Are Positively Associated with Visual–Spatial Functioning in Older Adults: An fMRI Study. (n.d.). Retrieved August 4, 2019, from https://www.mdpi.com/2072-6643/10/4/458
  30. Okunade, O., Niranjan, K., Ghawi, S. K., Kuhnle, G., & Methven, L. (2018). Supplementation of the Diet by Exogenous Myrosinase via Mustard Seeds to Increase the Bioavailability of Sulforaphane in Healthy Human Subjects after the Consumption of Cooked Broccoli. Molecular Nutrition & Food Research, 62(18), 1700980. https://doi.org/10.1002/mnfr.201700980
  31. Pivotal role of choline metabolites in remyelination | Brain | Oxford Academic. (n.d.). Retrieved August 4, 2019, from https://academic.oup.com/brain/article/138/2/398/293983
  32. Poly, C., Massaro, J. M., Seshadri, S., Wolf, P. A., Cho, E., Krall, E., … Au, R. (2011). The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort1234. The American Journal of Clinical Nutrition, 94(6), 1584–1591. https://doi.org/10.3945/ajcn.110.008938
  33. Ramlagan, P., Rondeau, P., Planesse, C., Neergheen-Bhujun, V. S., Bourdon, E., & Bahorun, T. (2017). Comparative suppressing effects of black and green teas on the formation of advanced glycation end products (AGEs) and AGE-induced oxidative stress. Food & Function, 8(11), 4194–4209. https://doi.org/10.1039/c7fo01038a
  34. Rendeiro, C., Vauzour, D., Kean, R. J., Butler, L. T., Rattray, M., Spencer, J. P. E., & Williams, C. M. (2012). Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology, 223(3), 319–330. https://doi.org/10.1007/s00213-012-2719-8
  35. Scholey, A., & Owen, L. (2013). Effects of chocolate on cognitive function and mood: a systematic review. Nutrition Reviews, 71(10), 665–681. https://doi.org/10.1111/nure.12065
  36. Sedlak, T. W., Nucifora, L. G., Koga, M., Shaffer, L. S., Higgs, C., Tanaka, T., … Sawa, A. (2017). Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Molecular Neuropsychiatry, 3(4), 214–222. https://doi.org/10.1159/000487639
  37. Skripuletz, T., Linker, R. A., & Stangel, M. (2015). The choline pathway as a strategy to promote central nervous system (CNS) remyelination. Neural Regeneration Research, 10(9), 1369–1370. https://doi.org/10.4103/1673-5374.165498
  38. Smit, H. J., Gaffan, E. A., & Rogers, P. J. (2004). Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology, 176(3), 412–419. https://doi.org/10.1007/s00213-004-1898-3
  39. Socci, V., Tempesta, D., Desideri, G., De Gennaro, L., & Ferrara, M. (2017). Enhancing Human Cognition with Cocoa Flavonoids. Frontiers in Nutrition, 4. https://doi.org/10.3389/fnut.2017.00019
  40. Subash, S., Essa, M. M., Al-Adawi, S., Memon, M. A., Manivasagam, T., & Akbar, M. (2014). Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regeneration Research, 9(16), 1557–1566. https://doi.org/10.4103/1673-5374.139483
  41. Tokuda, H., Kontani, M., Kawashima, H., Kiso, Y., Shibata, H., & Osumi, N. (2014). Differential effect of arachidonic acid and docosahexaenoic acid on age-related decreases in hippocampal neurogenesis. Neuroscience Research, 88, 58–66. https://doi.org/10.1016/j.neures.2014.08.002
  42. Varghese, S., Shameena, B., Lakshmy, P. S., Biju, M. P., Easwar Shankar, P. N., Paulose, C. S., & Oommen, O. V. (2001). Polyunsaturated fatty acids (PUFA) regulate neurotransmitter contents in rat brain. Indian Journal of Biochemistry & Biophysics, 38(5), 327–330.
  43. Vauzour, D., Vafeiadou, K., Rodriguez-Mateos, A., Rendeiro, C., & Spencer, J. P. E. (2008). The neuroprotective potential of flavonoids: a multiplicity of effects. Genes & Nutrition, 3(3–4), 115–126. https://doi.org/10.1007/s12263-008-0091-4
  44. Wang, J., Wu, N., & Yang, Y. (2016). Determination of Carotenoids in Egg Yolk by High Performance Liquid Chromatography with Vortex-Assisted Hollow Fiber Liquid-Phase Microextraction using Mixed Extraction Solvent. Journal of Chromatographic Science, 54(10), 1834–1840. https://doi.org/10.1093/chromsci/bmw130
  45. Yamagishi, S.-I., Matsui, T., Ishibashi, Y., Isami, F., Abe, Y., Sakaguchi, T., & Higashimoto, Y. (2017). Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System. Current Pharmaceutical Design, 23(8), 1135–1141. https://doi.org/10.2174/1381612822666161021155502
  46. Zeisel, S. H. (2004). Nutritional importance of choline for brain development. Journal of the American College of Nutrition, 23(6 Suppl), 621S-626S.