Ramberg J, Le L, McAnalley S, Koepke CM, Vennum E, McAnalley B GlycoScience & Nutrition 2003

1. Why Are Whole-Food Dietary Supplements Better than Single-Nutrient Supplements? A Review Based on the Vitamin C Literature Ramberg J, Le L, McAnalley S, Koepke CM, Vennum E,McAnalley B GlycoScience & Nutrition 2003 Vol. 4(4):1-8

2. Scurvy is the nutritional deficiency disease that has probably caused the most suffering in human history. Despite the fact that over 500 years ago certain foods – particularly citrus fruits – were known to cure scurvy, the disease continued to kill millions.1 WHY? 1. Carpenter KJ. The History of Scurvy and Vitamin C. Cambridge: Cambridge University Press, 1986.

3. In part, the efficacy of citrus fruits as a cure for scurvy was questioned when stored or processed fruit became ineffectual. In addition, people were not ready to accept the idea that, while citrus fruits might cure scurvy, a lack of citrus fruits could cause the disease. That is, the concept of a nutritional deficiency was unknown.1 1. Carpenter KJ. The History of Scurvy and Vitamin C. Cambridge: Cambridge University Press, 1986.

4. The chance discovery that guinea pigs could develop scurvy quickly gave scientists the tool they needed to prove that the disease was caused by a nutritional deficiency. The Hungarian scientist Szent-Gyorgyi isolated the active component, ascorbic acid, in 1932.

5. After 11 Nobel prizes were awarded for vitamin discoveries, the 20th Century became known as the “Golden Age of Nutrition”.

6. Once the importance of vitamin C was recognized, nutritionists naturally wondered if “more is better”. Thus, high-dose “solo” vitamin C supplementation was pursued.

7. We recently summarized these studies and high-dose studies of other antioxidant nutrients and reported that high dose supplementation of isolated nutrients may not be beneficial.2 2. Koepke CM et al. Results of clinical trials with antioxidants: a review. GlycoScience & Nutrition (Official Publication of GlycoScience com: The Nutrition Science Site). 2003;4(3):1-7.

8. A chance discovery by Szent-Gyorgyi in the 1930s presaged a nutritional concept that is gaining wide acceptance today. He noticed that in a certain disease condition intact lemon juice was curative when vitamin C alone was ineffective.3 3. Bensath A, et al. Vitamin nature of flavones. Nature. 1936;p798.

9. He then found that, in addition to vitamin C, intact lemon juice contained another important component, a flavonoid that he named “vitamin P”. Additional experiments confirmed that flavonoids help maintain levels of vitamin C in tissues.4,5 4. Rusznyak St., Szent-Gyorgyi A. Vitamin P: Flavanols as vitamins. Nature. 1936;133:27. 5. Ambrose AM, De Eds F. The value of rutin and quercetin in scurvy. J Nutr. 1949;38:305-317.

10. This fortuitous discovery most certainly solves a nutrition mystery that has persisted for almost 100 years. That is, why are lemons much more effective against scurvy than limes, even though they have just a little more vitamin C?

11. The answer? There must be something else in lemons that contributes to their anti-scurvy properties.

12. That “something else” is flavonoids. Lemons have over twice the amount of flavonoids (including Szent-Gyorgyi’s vitamin “P”) than the amount found in limes.6 6. Berhow M, Tisserat B, Kanes K, and Vandercook C. Survey of phenolic compounds produced in citrus. Technical Bulletin 1856, USDA: 1998.

14. What else do flavonoids do? They serve as antioxidants for vitamin C and vice-versa. Rutin (Szent-Gyorgyi’s vitamin P) and quercetin (closely related to Vitamin P) appear to provide the greatest protection.7 7. Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev. 2000;52(4):673-751.

15. They also have lipid-lowering, vasodilatory, anti-inflammatory, and anti-carcinogenic effects.8 8. Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995;33(12):1061-1080.

16. Now that thousands of the phytochemical compounds that plants produce have been characterized, we are ready to investigate their benefits for both the plants that produce them as well as the humans who eat them.

17. Plants use some of the nutrients they produce (including flavonoids and vitamins C and E) to cope with oxidative stress. When plants are stressed, they produce more of these phytonutrients.9 9. Demmig-Adams B, Adams WW, III. Antioxidants in photosynthesis and human nutrition. Science. 2002;298(5601):2149-2153.

18. When humans are stressed, they need to eat more of them. If they don’t, the consequences are significant.

19. People who eat fewer plant foods have a higher risk of diseases associated with increased oxidative stress, including cancers, pro-inflammatory diseases, autoimmune diseases, and neurological disorders.9 9. Demmig-Adams B, Adams WW, III. Antioxidants in photosynthesis and human nutrition. Science. 2002;298(5601):2149-2153.

20. Are citrus fruits the richest source of vitamin C? Actually, other foods have so much vitamin C, they make citrus fruits look deficient! The Australian bush plum (Terminalia ferdinandiana) wins the prize for being the richest known natural source of vitamin C in the world.10 10. Brand JC, Cherikoff V, Lee A, et al. An outstanding food source of vitamin C. Lancet. 1982;2(8303):873.

22. We know that flavonoids, present in all fruits and vegetables, are particularly abundant in citrus fruits. What other phytonutrients can be found in vitamin C-rich foods?

23. Ramberg J et al. Why are Natural Source Dietary Supplements Best? A Review Based on the Vitamin C Literature. GlycoScience & Nutrition (Official Publication of GlycoScience.com: the Nutrition Science Site) 2003;4(4):1-8.

24. Many of these nutrients function as antioxidants.

26. Some recent studies have measured exactly which nutrients can contribute to a food’s antioxidant “capacity”.

28. Many studies have shown that, unlike “solo” nutrients, combined nutrients provided in a form that mimics natural sources provide particular benefit. For example: Flavonoids and vitamin C combined are more effective and may be required in lower amounts than either “solo” nutrient.3,4,5,11,12,13 3. Bensath A, et al. Vitamin nature of flavones. Nature. 1936;p798. 4. Rusznyak St., Szent-Gyorgyi A. Vitamin P: Flavanols as vitamins. Nature. 1936;133:27. 5. Ambrose AM, De Eds F. The value of rutin and quercetin in scurvy. J Nutr. 1949;38:305-317 11. Kandaswami C, Perkins E, Soloniuk DS, et al. Ascorbic acid-enhanced antiproliferative effect of flavonoids on squamous cell carcinoma in vitro. Anticancer Drugs. 1993;4(1):91-96. 12. Vrijsen R, Everaert L, Boeye A. Antiviral activity of flavones and potentiation by ascorbate. J Gen Virol. 1988;69 ( Pt 7)(1749-1751. 13. Vinson JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988;48(3):601-604.

29. Foods are depleted of large amounts of numerous nutrients following storage, preparation, cooking, and processing.14 For those who strive for optimal nutrition, supplementation makes sense. 14. Ramberg J, McAnalley BH. From the farm to the kitchen table: a review of the nutrient losses in foods. GlycoScience & Nutrition (Official Publication of GlycoScience com: The Nutrition Science Site). 2002;3(5):1-12.

30. Freeze-drying is the best method for preserving many nutrients.15,16 15. Prinzo ZW. Scurvy and Its Prevention and Control in Major Emergencies. WHO/NHD/99.11, World Health Organization: 1999. 16. Wolfe KL, Liu RH. Apple peels as a value-added food ingredient. J Agric Food Chem. 2003;51(6):1676-1683.

31. Recent supplementation studies have taught us that high dose “solo” supplements can actually be harmful. We now have a more sophisticated understanding of the complexity of phytonutrients and their interactions.

32. When selecting dietary supplements, we should remember the lessons of history and choose those that are derived from whole-food sources.