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By: Mohammad S. El-Lulu
  Master of Clinical nutrition
      Palestine - Gaza
2
• Ascorbic acid, is a water-soluble micronutrient that is
  easily excreted from the body when not needed.
• Person's age and health status can dramatically change
  his or her need for vitamin C. (Levine M, 1986).

• Vitamin C is better absorbed in the presence of
  flavonoids.
• The buffered forms should combine vit-C with minerals
  like calcium, magnesium, or potassium. Buffered vit-C
  may be helpful for individuals who have stomach
  sensitivity (Worthington-Roberts B., Breskin M., 1984).

                                                        3
• The protective role of vitamin C can help our skin and
  gums from pinpoint hemorrhage (scurvy disease).
  Cardiovascular diseases, cancers, and joint diseases are
  all associated with vitamin C deficiency and can be partly
  prevented by optimal intake of vitamin C (Kurl S et al,
  2002).
• Vitamin C achieves much of its protective effect by
  functioning as an antioxidant and preventing oxygen-
  based damage to our cells. Structures that contain fat
  (like the lipoprotein molecules that carry fat around our
  body) are particularly dependent on vitamin C for
  protection (Reaven PD, Witztum JL: 1996).


                                                           4
• The vitamin C deficiency disease called scurvy (including
  bleeding gums and skin discoloration due to ruptured
  blood vessels).
• Poor wound healing.
• Weak immune function, including susceptibility to colds
  and other infections.
• The lining of respiratory tract depend heavily on vitamin
  C for protection, respiratory infection and other lung-
  related conditions can also be symptomatic of vitamin C
  deficiency (Englard S, Seifter S, 1986).


                                                          5
• At high supplemental doses involving 5 or more grams of
  vitamin C, diarrhea can result from the fluid in the
  intestine becoming too concentrated ("osmotic diarrhea").
• Large supplemental doses of vitamin C can also increase
  levels of uric acid in the urine, because vitamin C can be
  broken down into uric acid. However, it is not clear that
  increased uric acid in the urine can increase a person's
  risk of forming uric acid kidney stones.
• Vitamin C can increase a person's absorption of iron from
  plant foods (Levine M, Cantilena CC, Dhariwal KR,
  1995).

                                                           6
• Collagen is one type of fiber found within connective
  tissue. Collagen fibers are made from protein, and they
  are somewhat unusual in having large amounts of two
  amino acids, called hydroxylysine and hydroxyproline.
  These two amino acids seem to be important for
  formation of all types of collagen and are needed to
  provide the different collagen types with their appropriate
  amount of strength and flexibility.
• Vitamin C is required to change proline into
  hydroxyproline (the collagen form) and lysine into
  hydroxylysine (once again, the collagen form) (Mirhadi SA
  et al., 1990).


                                                            7
• Poor intake of vitamin C-rich vegetables and fruits is a
  common contributor to vitamin C deficiency.
• Smoking and exposure to second hand smoke also
  increase the risk of vitamin C deficiency.
• The body's immune and detoxification systems make
  special use of vitamin C, and overload in either of these
  systems can increase risk of deficiency.
• The immune system protect the body from infection,
  including white blood cells, complement proteins,
  interferons; and vitamin C is especially important in the
  function of these immune components (Groff JL, Gropper
  SS, Hunt SM, 1995).

                                                          8
• Most forms of cardiovascular disease, joint disease,
  cancer, eye disease, thyroid disease, liver disease, and
  lung disease require special emphasis on vitamin C
  intake. The process of aging itself requires special
  attention to vitamin C. In addition to these broader
  categories, several specific health conditions also require
  special emphasis on vitamin C. These specific health
  conditions include (Subar A., Block G., 1990):
• Acne and Alcoholism, Alzheimer disease and asthma.
• Autism, depression and diabetes.
• Irritable bowel disease and Parkinsonism.

                                                            9
According to National Academy of Sciences which established the
following (RDA) Recommended Dietary Allowances in 2000 for vitamin C:
    Age in years                Male                  Female
1-3 (adequate intake)                       15 mg
4-8 (adequate intake)                       25 mg
9-13                                        45 mg
14-18                           75 mg                   65 mg
19 and older                    90 mg                   75 mg
Pregnant females                                      80-85 mg
Lactating females                                    115-120 mg




                                                                    10
Food Sources
(adapted from world healthiest food; WHFood’s)
               Food              Serving size   Calories   Vit-C (mg)
Bell peppers, red, raw, slices      1 cup        24.8        174.8
Broccoli, steamed                   1 cup        43.7        123.4
Strawberries                        1 cup        43.2        81.70
Lemon juice, fresh                 ¼ cup         15.3        28.06
Grapefruit                         ½ each        36.9        46.86
Kiwifruit                          1 each        46.4        57.00
Cantaloupe                          1 cup        56.0        67.52
Oranges                            1 each        61.6        69.70
Tomato, ripe                        1 cup        37.8        34.38
Banana                             1 each        108.1       10.75
Apples                             1 each        81.4        7.87
Grapes                              1 cup        61.6        3.68
Avocado, slices                     1 cup         235        11.53
                                                                     11
12
• Every 500 mg increase in vitamin C intake, a man’s risk
  of gout was cut by 17 percent. And for men with vitamin
  C intakes of at least 1,500 mg/day, the risk of gout was
  cut by 45 percent, said the findings of a prospective study
  with 46,994 men.
• Mechanism: Vitamin C may reduce levels of uric acid in
  the blood, thereby preventing the formation of the urate
  crystal. This may be achieved by vitamin C having an
  effect on the reabsorption of uric acid by the kidneys.
  This would increase the speed at which the kidneys work
  or protect against inflammation, all of which may reduce
  gout risk, they added (Choi H.K., Gao X., Curhan G.,
  2009).

                                                           13
• Block and her co-workers recruited 242 women aged between
  18 and 21. Two-thirds of the women were African-American,
  while the other third was Caucasian. The blood levels of
  vitamin C of the women ranged from 0.22 to 3.13 mg/dL.
• During follow-up over a ten year period, the researchers noted
  that blood vitamin C levels were inversely associated with both
  systolic and diastolic blood pressure.
• Mechanism: due to potential role for vitamin C via an
  antioxidant mechanism, there is also possibility other
  functions. These include a role in the function of smooth
  muscle function, or prevention of nitric oxide which is a
  vasodilator or compound that opens up the blood vessels
  (Block G et al., 2008).


                                                               14
• Vitamin C deficiency in the first weeks and months of life may
  impair the development of neurones in the brain, and
  decrease spatial memory, says an animal study from
  Denmark.
• The Danish researchers took 30 new born guinea pigs and
  randomly assigned them to one of two groups: One group was
  fed a vitamin C-sufficient diet, while the other group was fed
  the same diet but low in vitamin C. Levels of vitamin produced
  deficiency, but were not extreme enough to cause scurvy.
• After two months, the animals were tested in a water maze,
  and hippocampal neuron numbers were measured. Prof
  Lykkesfeldt and his co-workers report that the vitamin C
  deficient animals had a lower number of neurons in the
  hippocampus, and also performed worse in the maze tests
  (Lykkesfeldt J. et al., 2009).
• Increased intakes of vitamin C may increase the risk of
  developing cataracts in some elderly people, according to a
  new study.
• Findings from 24,593 Swedish women aged between 49 and
  83 indicated that vitamin C use was associated with a 25
  percent increase in the incidence of cataracts.
• Among the older women – over the age of 68 – vitamin C
  supplements were associated with a 38 percent increase in
  the risk of cataracts, report the researchers in the American
  Journal of Clinical Nutrition.
• The findings were further complicated in women on hormone
  replacement therapy, where the supplements were associated
  with a 56 percent increase in cataracts (Rautiainen S. et al.,
  2009).
                                                              16
• Higher levels of vitamin C from the diet may reduce the
  loss of bone mineral density in elderly men.
Protective mechanism:
• Sahni and co-workers state protective effects of vitamin
  C for bone health could be expected since the vitamin
  could counter the effects of oxidative stress, which plays
  a role in weakening of the bone by resorption.
• Furthermore, vitamin C plays an important role in the
  formation of collagen, which constitutes 90 percent of the
  bone matrix (Sahni S. et al., 2008).


                                                          17
• Vitamin C may reduce the effectiveness of chemotherapy
  by protecting the cancer cells.
• Using lymphoma and leukemia cell lines with and without
  pre-exposure to dehydroascorbic acid (DHA), Heaney
  and his co-workers investigated the effects of the anti-
  cancer drugs doxorubicin, cisplatin, vincristine,
  methotrexate, and imatinib.
• They found that the efficacy of the chemotherapy drugs
  tested was greatly reduced if the cells were pre-treated
  with vitamin C, compared to untreated cancer cells.
  Indeed, the reduction ranged from 30 to 70 percent,
  report the researchers (Heany et al., 2008).

                                                        18
• Administration of a physiological dose of [6S]-5-MTHF
• [6S]-5-methyl-tetra-hydro-folate with L-ascorbic acid
  significantly improved the measured serum folate
  response in folate saturated healthy men.
• When [6S]-5-MTHF was concurrently administered with
  289.4 or 973.8 mg [vitamin C], the total serum folate
  response was significantly improved (46.54.0 and
  53.04.0 versus 34.33.8 h nmol/l) (Verlinde P.H.C.J et al.,
  2007).




                                                          19
• Increased blood levels of vitamin C may reduce the risk
  of developing diabetes by 62 percent, says a study from
  Cambridge.
• “Fruit and vegetable consumption may be protective for
  diabetes risk, at least partially, through its effect on
  obesity.”
• Oxidative stress, the situation in which an imbalance
  between the levels of reactive oxygen species and
  antioxidants exists, can lead to disturbed glucose
  metabolism and hyperglycaemia (Harding A. et al).


                                                        20
• Increased blood levels of vitamin C may reduce the risk of
  stroke by 42 percent, suggests a large European-based study.
• Strokes occur when blood clots or an artery bursts in the brain
  and interrupts the blood supply to a part of the brain.
• Myint and co-workers followed the subjects for 9.5 years and
  documented 448 strokes during this time. The subjects
  completed a health and lifestyle questionnaire at the start of
  the study, and blood samples were taken to measure vitamin
  C levels.
• The highest average blood levels of vitamin C (greater than 66
  micromoles/litre) were associated with a 42 percent lower risk
  of stroke, compared to the lowest average blood levels (less
  than 41 micromoles/litre) (Myint P.K.et al, 2008).


                                                               21
References:
•   Block G, Jensen C.D., Norkus E.P., Hudes M., Crawford P.B., (2008). Vitamin C in plasma is
    inversely related to blood pressure and change in blood pressure during the previous year in young
    Black and White women. Nutrition Journal. 7:35 doi:10.1186/1475-2891-7-35.
•   Choi H.K, Gao X., Curhan G., (2009). Vitamin C Intake and the Risk of Gout in Men: A Prospective
    Study. Archives of internal medicine. 169 (5): 502-507.
•   Englard S, Seifter S (1986). The biological functions of ascorbic acid. Ann Rev Nutr 1986;6:365-
    406.
•   Groff JL, Gropper SS, Hunt SM (1995). Advanced Nutrition and Human Metabolism. West
    Publishing Company, New York, 1995.
•   Harding A.-H, Wareham N.J., Bingham S.A., Khaw K., Luben R., Welch A., Forouhi N.G. Plasma
    Vitamin C Level, Fruit and Vegetable Consumption, and the Risk of New-Onset Type 2 Diabetes
    Mellitus - The European Prospective Investigation of Cancer - Norfolk Prospective Study. Archives
    of Internal Medicine. 168 (14): 1493-1499.
•   Heaney M.L., Gardner J.R., Karasavvas N., Golde D.W., Scheinberg D.A., Smith E.A., O’Connor
    O.A, (2008). Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs. Cancer
    Research. Volume 68: 8031-8038. doi: 10.1158/0008-5472.CAN-08-1490.
•   Kurl S, Tuomainen TP, Laukkanen JA et al (2002). Plasma vitamin C modifies the association
    between hypertension and risk of stroke. Stroke 2002 Jun;33(6):1568-73.
•   Levine M (1986). New concepts in biology and biochemistry of ascorbic acid. N Engl J Med
    1986;314:892-902.
•   Levine M, Cantilena CC, Dhariwal KR (1995). Determination of optimal vitamin C requirements in
    humans. Am J Clin Nutr 1995;62(suppl):1347S-1356S.


                                                                                                   22
References:
•   Lykkesfeldt J., Tveden-Nyborg P., Johansen L.K., Raida Z., Villumsen C.K., Larsen J.O., (2009).
    Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of
    hippocampal neurons in guinea pigs. American Journal of Clinical Nutrition. doi:
    10.3945/ajcn.2009.27954.
•   Mirhadi SA, Singh S, Gupta PP (1990). Effect of Garlic Supplementation to Atherogenic Diet on
    Collagen Biosynthesis in Various Tissues of Rabbits. Indian Heart J.;42(2):99-104.
•   Myint P.K., Luben R.N., Welch A.A., Bingham S.A., Wareham N.J., Khaw K.-T, (2008). Fruit and
    vegetables: think variety, go ahead, eat!. American Journal of Clinical Nutrition. Volume 87: 5-7.
•   Rautiainen S., Ejdervik Lindblad B., Morgenstern R., Wolk A., (2009). Vitamin C supplements and
    the risk of age-related cataract: a population-based prospective cohort study in women.
    doi:10.3945/ajcn.2009.28528.
•   Reaven PD, Witztum JL (1996). Oxidized low density lipoproteins in atherogenesis: role of dietary
    modification. Ann Rev Nutr 1996;16:51-71.
•   Sahni S., Hannan M.T., Gagnon D., Blumberg J., Cupples L.A., Kiel D.P., Tucker K.L., (2008). High
    vitamin C intake is associated with lower 4-year bone loss in elderly men. Journal of Nutrition.
    Volume 138: 1931-1938.
•   Subar A, Block G (1990). Use of vitamin and mineral supplements. Am J Epidem 1990;132:1901-
    1011.
•   Worthington-Roberts B, Breskin M (1984). Supplementation patterns of Washington State
    dietitians. J Am Diet Assoc 1984;84(7):795-800.
•   Verlinde P.H.C.J., Oey I., Hendrickx A.M., Van Loey A.M., Temme E.H.M., (2007). L-ascorbic acid
    improves the serum folate response to an oral dose of [6S]-5-methyltetrahydrofolic acid in healthy
    men. European Journal of Clinical Nutrition. doi: 10.1038/sj.ejcn.1602840.

                                                                                                   23
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Vitamin C

  • 1. By: Mohammad S. El-Lulu Master of Clinical nutrition Palestine - Gaza
  • 2. 2
  • 3. • Ascorbic acid, is a water-soluble micronutrient that is easily excreted from the body when not needed. • Person's age and health status can dramatically change his or her need for vitamin C. (Levine M, 1986). • Vitamin C is better absorbed in the presence of flavonoids. • The buffered forms should combine vit-C with minerals like calcium, magnesium, or potassium. Buffered vit-C may be helpful for individuals who have stomach sensitivity (Worthington-Roberts B., Breskin M., 1984). 3
  • 4. • The protective role of vitamin C can help our skin and gums from pinpoint hemorrhage (scurvy disease). Cardiovascular diseases, cancers, and joint diseases are all associated with vitamin C deficiency and can be partly prevented by optimal intake of vitamin C (Kurl S et al, 2002). • Vitamin C achieves much of its protective effect by functioning as an antioxidant and preventing oxygen- based damage to our cells. Structures that contain fat (like the lipoprotein molecules that carry fat around our body) are particularly dependent on vitamin C for protection (Reaven PD, Witztum JL: 1996). 4
  • 5. • The vitamin C deficiency disease called scurvy (including bleeding gums and skin discoloration due to ruptured blood vessels). • Poor wound healing. • Weak immune function, including susceptibility to colds and other infections. • The lining of respiratory tract depend heavily on vitamin C for protection, respiratory infection and other lung- related conditions can also be symptomatic of vitamin C deficiency (Englard S, Seifter S, 1986). 5
  • 6. • At high supplemental doses involving 5 or more grams of vitamin C, diarrhea can result from the fluid in the intestine becoming too concentrated ("osmotic diarrhea"). • Large supplemental doses of vitamin C can also increase levels of uric acid in the urine, because vitamin C can be broken down into uric acid. However, it is not clear that increased uric acid in the urine can increase a person's risk of forming uric acid kidney stones. • Vitamin C can increase a person's absorption of iron from plant foods (Levine M, Cantilena CC, Dhariwal KR, 1995). 6
  • 7. • Collagen is one type of fiber found within connective tissue. Collagen fibers are made from protein, and they are somewhat unusual in having large amounts of two amino acids, called hydroxylysine and hydroxyproline. These two amino acids seem to be important for formation of all types of collagen and are needed to provide the different collagen types with their appropriate amount of strength and flexibility. • Vitamin C is required to change proline into hydroxyproline (the collagen form) and lysine into hydroxylysine (once again, the collagen form) (Mirhadi SA et al., 1990). 7
  • 8. • Poor intake of vitamin C-rich vegetables and fruits is a common contributor to vitamin C deficiency. • Smoking and exposure to second hand smoke also increase the risk of vitamin C deficiency. • The body's immune and detoxification systems make special use of vitamin C, and overload in either of these systems can increase risk of deficiency. • The immune system protect the body from infection, including white blood cells, complement proteins, interferons; and vitamin C is especially important in the function of these immune components (Groff JL, Gropper SS, Hunt SM, 1995). 8
  • 9. • Most forms of cardiovascular disease, joint disease, cancer, eye disease, thyroid disease, liver disease, and lung disease require special emphasis on vitamin C intake. The process of aging itself requires special attention to vitamin C. In addition to these broader categories, several specific health conditions also require special emphasis on vitamin C. These specific health conditions include (Subar A., Block G., 1990): • Acne and Alcoholism, Alzheimer disease and asthma. • Autism, depression and diabetes. • Irritable bowel disease and Parkinsonism. 9
  • 10. According to National Academy of Sciences which established the following (RDA) Recommended Dietary Allowances in 2000 for vitamin C: Age in years Male Female 1-3 (adequate intake) 15 mg 4-8 (adequate intake) 25 mg 9-13 45 mg 14-18 75 mg 65 mg 19 and older 90 mg 75 mg Pregnant females 80-85 mg Lactating females 115-120 mg 10
  • 11. Food Sources (adapted from world healthiest food; WHFood’s) Food Serving size Calories Vit-C (mg) Bell peppers, red, raw, slices 1 cup 24.8 174.8 Broccoli, steamed 1 cup 43.7 123.4 Strawberries 1 cup 43.2 81.70 Lemon juice, fresh ¼ cup 15.3 28.06 Grapefruit ½ each 36.9 46.86 Kiwifruit 1 each 46.4 57.00 Cantaloupe 1 cup 56.0 67.52 Oranges 1 each 61.6 69.70 Tomato, ripe 1 cup 37.8 34.38 Banana 1 each 108.1 10.75 Apples 1 each 81.4 7.87 Grapes 1 cup 61.6 3.68 Avocado, slices 1 cup 235 11.53 11
  • 12. 12
  • 13. • Every 500 mg increase in vitamin C intake, a man’s risk of gout was cut by 17 percent. And for men with vitamin C intakes of at least 1,500 mg/day, the risk of gout was cut by 45 percent, said the findings of a prospective study with 46,994 men. • Mechanism: Vitamin C may reduce levels of uric acid in the blood, thereby preventing the formation of the urate crystal. This may be achieved by vitamin C having an effect on the reabsorption of uric acid by the kidneys. This would increase the speed at which the kidneys work or protect against inflammation, all of which may reduce gout risk, they added (Choi H.K., Gao X., Curhan G., 2009). 13
  • 14. • Block and her co-workers recruited 242 women aged between 18 and 21. Two-thirds of the women were African-American, while the other third was Caucasian. The blood levels of vitamin C of the women ranged from 0.22 to 3.13 mg/dL. • During follow-up over a ten year period, the researchers noted that blood vitamin C levels were inversely associated with both systolic and diastolic blood pressure. • Mechanism: due to potential role for vitamin C via an antioxidant mechanism, there is also possibility other functions. These include a role in the function of smooth muscle function, or prevention of nitric oxide which is a vasodilator or compound that opens up the blood vessels (Block G et al., 2008). 14
  • 15. • Vitamin C deficiency in the first weeks and months of life may impair the development of neurones in the brain, and decrease spatial memory, says an animal study from Denmark. • The Danish researchers took 30 new born guinea pigs and randomly assigned them to one of two groups: One group was fed a vitamin C-sufficient diet, while the other group was fed the same diet but low in vitamin C. Levels of vitamin produced deficiency, but were not extreme enough to cause scurvy. • After two months, the animals were tested in a water maze, and hippocampal neuron numbers were measured. Prof Lykkesfeldt and his co-workers report that the vitamin C deficient animals had a lower number of neurons in the hippocampus, and also performed worse in the maze tests (Lykkesfeldt J. et al., 2009).
  • 16. • Increased intakes of vitamin C may increase the risk of developing cataracts in some elderly people, according to a new study. • Findings from 24,593 Swedish women aged between 49 and 83 indicated that vitamin C use was associated with a 25 percent increase in the incidence of cataracts. • Among the older women – over the age of 68 – vitamin C supplements were associated with a 38 percent increase in the risk of cataracts, report the researchers in the American Journal of Clinical Nutrition. • The findings were further complicated in women on hormone replacement therapy, where the supplements were associated with a 56 percent increase in cataracts (Rautiainen S. et al., 2009). 16
  • 17. • Higher levels of vitamin C from the diet may reduce the loss of bone mineral density in elderly men. Protective mechanism: • Sahni and co-workers state protective effects of vitamin C for bone health could be expected since the vitamin could counter the effects of oxidative stress, which plays a role in weakening of the bone by resorption. • Furthermore, vitamin C plays an important role in the formation of collagen, which constitutes 90 percent of the bone matrix (Sahni S. et al., 2008). 17
  • 18. • Vitamin C may reduce the effectiveness of chemotherapy by protecting the cancer cells. • Using lymphoma and leukemia cell lines with and without pre-exposure to dehydroascorbic acid (DHA), Heaney and his co-workers investigated the effects of the anti- cancer drugs doxorubicin, cisplatin, vincristine, methotrexate, and imatinib. • They found that the efficacy of the chemotherapy drugs tested was greatly reduced if the cells were pre-treated with vitamin C, compared to untreated cancer cells. Indeed, the reduction ranged from 30 to 70 percent, report the researchers (Heany et al., 2008). 18
  • 19. • Administration of a physiological dose of [6S]-5-MTHF • [6S]-5-methyl-tetra-hydro-folate with L-ascorbic acid significantly improved the measured serum folate response in folate saturated healthy men. • When [6S]-5-MTHF was concurrently administered with 289.4 or 973.8 mg [vitamin C], the total serum folate response was significantly improved (46.54.0 and 53.04.0 versus 34.33.8 h nmol/l) (Verlinde P.H.C.J et al., 2007). 19
  • 20. • Increased blood levels of vitamin C may reduce the risk of developing diabetes by 62 percent, says a study from Cambridge. • “Fruit and vegetable consumption may be protective for diabetes risk, at least partially, through its effect on obesity.” • Oxidative stress, the situation in which an imbalance between the levels of reactive oxygen species and antioxidants exists, can lead to disturbed glucose metabolism and hyperglycaemia (Harding A. et al). 20
  • 21. • Increased blood levels of vitamin C may reduce the risk of stroke by 42 percent, suggests a large European-based study. • Strokes occur when blood clots or an artery bursts in the brain and interrupts the blood supply to a part of the brain. • Myint and co-workers followed the subjects for 9.5 years and documented 448 strokes during this time. The subjects completed a health and lifestyle questionnaire at the start of the study, and blood samples were taken to measure vitamin C levels. • The highest average blood levels of vitamin C (greater than 66 micromoles/litre) were associated with a 42 percent lower risk of stroke, compared to the lowest average blood levels (less than 41 micromoles/litre) (Myint P.K.et al, 2008). 21
  • 22. References: • Block G, Jensen C.D., Norkus E.P., Hudes M., Crawford P.B., (2008). Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women. Nutrition Journal. 7:35 doi:10.1186/1475-2891-7-35. • Choi H.K, Gao X., Curhan G., (2009). Vitamin C Intake and the Risk of Gout in Men: A Prospective Study. Archives of internal medicine. 169 (5): 502-507. • Englard S, Seifter S (1986). The biological functions of ascorbic acid. Ann Rev Nutr 1986;6:365- 406. • Groff JL, Gropper SS, Hunt SM (1995). Advanced Nutrition and Human Metabolism. West Publishing Company, New York, 1995. • Harding A.-H, Wareham N.J., Bingham S.A., Khaw K., Luben R., Welch A., Forouhi N.G. Plasma Vitamin C Level, Fruit and Vegetable Consumption, and the Risk of New-Onset Type 2 Diabetes Mellitus - The European Prospective Investigation of Cancer - Norfolk Prospective Study. Archives of Internal Medicine. 168 (14): 1493-1499. • Heaney M.L., Gardner J.R., Karasavvas N., Golde D.W., Scheinberg D.A., Smith E.A., O’Connor O.A, (2008). Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs. Cancer Research. Volume 68: 8031-8038. doi: 10.1158/0008-5472.CAN-08-1490. • Kurl S, Tuomainen TP, Laukkanen JA et al (2002). Plasma vitamin C modifies the association between hypertension and risk of stroke. Stroke 2002 Jun;33(6):1568-73. • Levine M (1986). New concepts in biology and biochemistry of ascorbic acid. N Engl J Med 1986;314:892-902. • Levine M, Cantilena CC, Dhariwal KR (1995). Determination of optimal vitamin C requirements in humans. Am J Clin Nutr 1995;62(suppl):1347S-1356S. 22
  • 23. References: • Lykkesfeldt J., Tveden-Nyborg P., Johansen L.K., Raida Z., Villumsen C.K., Larsen J.O., (2009). Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. American Journal of Clinical Nutrition. doi: 10.3945/ajcn.2009.27954. • Mirhadi SA, Singh S, Gupta PP (1990). Effect of Garlic Supplementation to Atherogenic Diet on Collagen Biosynthesis in Various Tissues of Rabbits. Indian Heart J.;42(2):99-104. • Myint P.K., Luben R.N., Welch A.A., Bingham S.A., Wareham N.J., Khaw K.-T, (2008). Fruit and vegetables: think variety, go ahead, eat!. American Journal of Clinical Nutrition. Volume 87: 5-7. • Rautiainen S., Ejdervik Lindblad B., Morgenstern R., Wolk A., (2009). Vitamin C supplements and the risk of age-related cataract: a population-based prospective cohort study in women. doi:10.3945/ajcn.2009.28528. • Reaven PD, Witztum JL (1996). Oxidized low density lipoproteins in atherogenesis: role of dietary modification. Ann Rev Nutr 1996;16:51-71. • Sahni S., Hannan M.T., Gagnon D., Blumberg J., Cupples L.A., Kiel D.P., Tucker K.L., (2008). High vitamin C intake is associated with lower 4-year bone loss in elderly men. Journal of Nutrition. Volume 138: 1931-1938. • Subar A, Block G (1990). Use of vitamin and mineral supplements. Am J Epidem 1990;132:1901- 1011. • Worthington-Roberts B, Breskin M (1984). Supplementation patterns of Washington State dietitians. J Am Diet Assoc 1984;84(7):795-800. • Verlinde P.H.C.J., Oey I., Hendrickx A.M., Van Loey A.M., Temme E.H.M., (2007). L-ascorbic acid improves the serum folate response to an oral dose of [6S]-5-methyltetrahydrofolic acid in healthy men. European Journal of Clinical Nutrition. doi: 10.1038/sj.ejcn.1602840. 23
  • 24. 24