Cod Liver Oil

1. Cod Liver Oil Our Number One Superfood! Regional Wise Traditions September 2013, Portland, OR The content of this talk is the independent work of Chris Masterjohn, PhD, and does not necessarily represent the positions or opinions of the University of Illinois. Chris Masterjohn, PhD

2. Pliny the Elder, Natural History, 73 ADLichens and Leprosy “Some persons bake dolphin's liver in an earthen vessel, till a grease flows therefrom like oil in appearance: this they use by way of ointment for these diseases."

3. John Hughes Bennett, 1841Treatise on Cod Liver Oil • Introduced systematic use of microscope and study of histology to medical curricula. • Opposed indiscriminate use of drugs, bleeding, and mercury. • Proved the κώνειον used to execute Socrates was hemlock. • First to describe leukemia as a blood disorder. “The Cod liver oil appears to have been used immemorially as a popular remedy for the cure of rheumatism in various countries. In Sweden and Norway . . . Germany . . . Holland . . . Scotland . . .”

4. Scrofula – Tuberculosis of the Lymph Nodes in the Neck • Common blood deficiency underlying scrofula and rickets in children and osteomalacia, gout, and rheumatism in adults. • Cod liver oil was an effective remedy.

5. Cod Liver Oil Appeared to Be a Successful Treatment For Tuberculosis Hospital for Consumption and Diseases of the Chest. The First Medical Report of the Hospitalfor Consumption and Diseases of the Chest, presented to the Committee of Management bythe Physicians of the Institution. J Churchill, 1849, pp. 31-41.

6. Late Nineteenth Century US Cod Liver Oil Imports: ~2 Million Lbs/Yr

7. Did Cod Liver Oil Contribute to the Eradication of Tuberculosis Mortality? Use of CLO as a Treatment Thomas McKeown, The Modern Rise of Population, 1976.

8. Similar Decline in Tuberculosis Mortality in the United States Death rate per 1000 individuals. McKinlay JB and McKinlay SM. The Questionable Contribution of Medical Measures to the Decline of Mortality in the United States in the Twentieth Century. The Millbank Memorial Fund Quarterly. Health and Society. 1977;55(3):405-428.

9. Deficiency Diseases of Vitamins A and D Discovered Discovered 1910s and 1920s Corneal ulceration due to xerophthalmia, prevented and cured by vitamin A. Bowed and poorly mineralized legs due to rickets, prevented and cured by vitamin D.

10. Dogs Fed Vitamin A-Deficient Diets Developed Pneumonia Soft bones, partially collapsed lungs, bronchial pneumonia. Olive Oil Soft bones, partially collapsed lungs, free of infection. Butter (A) Well mineralized bones, fully functioning lungs, free of infection. Cod Liver Oil (A+D) Green HN, Mellanby E. Vitamin A as an Anti-Infective Agent. BMJ. 1928;2:691-6.

11. Vitamin A, Not Vitamin D, Protected Against Infection in Rats Infection (tongue, throat, eyes, lungs, GI tract) Vitamin-Deficient Diet (Heated Casein, Rice Starch, Sugar, Olive Oil, Lemon Juice, Mineral Salts) Hastened onset of infection Diet Plus Vitamin D2 Diet Plus D2 and Vitamin A (Dried Cabbage, Butter, or Cod Liver Oil) No Infection Diet Plus Vitamin A No Infection Green HN, Mellanby E. Vitamin A as an Anti-Infective Agent. BMJ. 1928;2:691-6.

12. Cod Liver Oil Decreases the Incidence of Colds One tbsp CLO (15,000 IU A; 2,000 IU D) per day, Dec-March, n=313. Holmes AD, Pigott MG, Sawyer WA, Comstock L. Vitamins Aid Reduction of Lost Time in Industry. Indust Eng Chem. 1932;24:1058-60.

13. Cod Liver Oil Decreases Time Missed From Work One tbsp CLO (15,000 IU A; 2,000 IU D) per day, Dec-March, n=313. Holmes AD, Pigott MG, Sawyer WA, Comstock L. Vitamins Aid Reduction of Lost Time in Industry. Indust Eng Chem. 1932;24:1058-60.

14. Cod Liver Oil Concentrate Reduces Measles Mortality Over Half Ellison JB. Intensive Vitamin Therapy in Measles. BMJ. 1932;2:708-11.

15. Cod Liver Oil Was Widely Promoted in the 1920s and 1930s

16. Massive Increase in US Cod Liver Oil Imports 1922-1939 USDA Statistical Bulletin No. 376, U.S. Fats and Oils Statistics, 1909-65: Oilseeds, Oils and Meals, Animal Fats and Oils, Food Fats, Nonfood Fats.

17. Did Cod Liver Oil Contribute to the Eradication of Tuberculosis Mortality? Use of CLO as a Treatment Identification of Fat-Soluble Vitamins Vitamin A as “Anti-Infective” Thomas McKeown, The Modern Rise of Population, 1976.

18. Did Cod Liver Oil Contribute to the Eradication of Measles Mortality? Identification of Fat-Soluble Vitamins Vitamin A as “Anti-Infective” Thomas McKeown, The Modern Rise of Population, 1976.

19. Did Cod Liver Oil Contribute to the Eradication of Measles Mortality? Identification Of Fat-Soluble Vitamins Vitamin A as “Anti-Infective” McKinlay JB and McKinlay SM. The Questionable Contribution of Medical Measures to the Decline of Mortality in the United States in the Twentieth Century. The Millbank Memorial Fund Quarterly. Health and Society. 1977;55(3):405-428.

20. Two Worlds Collide: Antibiotics Replace Interest in Cod Liver Oil Prontosil Vitamin A University of Wisconsin, Madison Heinrich Himmler, head of all Nazi police and security forces, touring an IG Farben facility

21. US Cod Liver Oil Imports Declined After World War II USDA Statistical Bulletin No. 376, U.S. Fats and Oils Statistics, 1909-65: Oilseeds, Oils and Meals, Animal Fats and Oils, Food Fats, Nonfood Fats.

22. Time Magazine – July 15, 1946“Hardier Germs” “Though bacterial ‘drug-fastness’ is a serious problem for medical researchers, Dr. Molitor believes there is yet no cause for public anxiety. Bacteria do not always keep up their resistance. Some bacteria, as they become drug-resistant, also become less virulent; and new antibiotics are being discovered all the time. The adaptable researchers hope to keep two jumps ahead of the jump-ahead germs.” “Just when the sulfa drugs, penicillin and the other antibiotics seemed to be sweeping most of the bacterial diseases before them, a dark thunderhead of rumor appeared on the horizon—the germs were rallying and fighting back.”

23. Weston Price Had Foreshadowed Antibiotic Resistance in 1923 “... strains were planted in a culture medium in which they were known to grow well, and to this medium, toxic substances were added to determine the point at which the toxicity would prevent the growth of the organisms. It was found that by taking the dilution just greater than would entirely inhibit the growth of the organism and maintaining the organisms in that concentration, they presently acquired a quality of growing quite readily in the presence of that poison; and by replanting, it was found that they would soon permit a new increase without seriously handicapping them.” –Weston Price, Dental Infections Oral and Systemic, 1923

24. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

25. Does Vitamin A Increase Mortality? In trials with low risk of bias, beta-carotene and vitamin E significantly increased mortality, whereas vitamin A, vitamin C, and selenium did not significantly affect mortality. In univariate meta-regression analysis, the dose of vitamin A was significantly associated with increased mortality (RR 1.0006). Over 240 pages Only two studies on vitamin A as a single treatment

26. First Study: No Effect on Mortality First Study: 25,000 IU/d Vitamin A Decreases Squamous Cell Carcinoma by 24% Moon TE, Levine N, Cartmel B, et al. Effect of Retinol in Preventing Squamous Cell Skin Cancer in Moderate-Risk Subjects: A Randomized, Double-Blind, Controlled Trial. Cancer Epidemiol Biomarkers Prev. 1997;6(11):949-56.

27. Second Study Showed the Number One Cause of Death is… Second Study Showed the Number One Cause of Death is Getting Old! Subjects Receiving Vitamin A Were on Average 5 Years Older! Murphy S, West Jr. KP, Greenbough III WB, Cherot E, Katz J, Clement L. Impact of vitamin A supplementation on the incidence of infection in elderly nursing-home residents: a randomized controlled trial. Age Ageing. 1992;21(6):435-9.

28. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

29. Does Vitamin A Increase the Risk of Infection in Developed Countries? • One study was conducted in Ecuador; the other was conducted in Indonesia. • Both studies measured serum retinol. • Neither study reported an association between the effect of vitamin A and serum retinol status. • Sempertegui F,, Estrella B, Camaniero V, et al. The Beneficial Effects of Weedly Low-dose Vitamin A Supplementation on Acute Lower Respiratory Infections and Diarrhea in Ecuadorian Children. Pediatrics. 1999;104(1):e1. • Dibley MJ, Sadjimin T, Kjolhede CL, Moulton LH. Vitamin A Supplementation Fails to Reduce Incidence of Acute Respiratory Illness and Diarrhea in Preschool-Age Indonesian Children. J Nutr. 1996;126:434-42.

30. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

31. Vitamin A Intake Tied to Birth Defects, But No More Than in the General Population Watkins M, Moore C, Mulinare J. Teratogenicity of High Vitamin A Intake. N Engl J Med. 1996;334:1197.

32. Vitamin A Intake Tied to Birth Defects, But No More Than in the General Population Multivitamins and fortified breakfast cereals? Watkins M, Moore C, Mulinare J. Teratogenicity of High Vitamin A Intake. N Engl J Med. 1996;334:1197.

33. Vitamin A Supplementation Up to 40,000 IU Tied to Lower Risk of Birth Defects Martinez-Frias ML, Salvardor J. Epidemiological Aspects of Prenatal Exposure to High Doses of Vitamin A in Spain. Eur J Epidemiol. 1990;6(2):118-123.

34. Vitamin A Supplementation Tied to Lower Risk of Major Malformations Mastriacovo P, Mazzone T, Addis A, Elephant E, Carlier P, Vial T. High vitamin A intake in early pregnancy and major malformations: a multicenter prospective controlled study. Teratology. 1999. 59(1):7-11.

35. Two Negative Studies • No association between a multivitamin + 10,000 IU vitamin A and risk of birth defects. Shaw GM, Wasserman CR, Block G. High maternal vitamin A intake and risk of anomalies of structures with cranial neural crest cell contribution. Lancet. 1996;347:899-900. • No association between the use of vitamin A in supplements, fortified breakfast cereal, organ meats, or liver. Mills JL, Simpson JL, Cunningham GC, Conley MR, Rhoads GG, Vitamin A and birth defects. Am J Obstet Gynecol. 1997;177(1):31-6.

36. Limitations of These Studies Epidemiological (observational) studies can be used to generate hypotheses, but experimentation must confirm them. Most of the studies did not differentiate the source of vitamin A. Interaction with vitamin D? Implications Limited to Early Pregnancy (~ 8 wks).

37. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

38. Vitamin A Causes a Small Decrease in Serum Calcium * p<0.05 vs. placebo ** p<0.01 vs. placebo + p<0.05 vs. vitamin D D A+D PlaceboA Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res. 2001;16(10):1899-905.

39. Low Serum Ca2+ Increases PTH, Leading to Bone Resorption

40. The 25(OH)D Level that Maximally Suppresses PTH Is Considered Optimal Chapuy et al. Osteoporosis Int. 1997;439-443.

41. Vitamin A Does Not Antagonize Calcitriol Suppression of PTH * p<0.05 vs. placebo ** p<0.01 vs. placebo + p<0.05 vs. vitamin D APlacebo DA+D

42. Vitamin A Does Not Increase Bone Resorption PlaceboAD/A+D

43. Vitamins A and D Only Protect Against Colds When Combined 54 “chronic or frequent cold sufferers” aged 7-49 given 9,000-40,000 IU A, 120,000-300,000 IU D, or both, daily Sept-June for three years. Spiesman IG. Massive does of vitamins A and D in the prevention of the common cold. Arch Otolaryngol.1941;34(4):787-791.

44. Vitamins A and D Proved Toxic Alone But Not in Combination Percentage of Subjects Who Developed Symptoms of Toxicity 54 “chronic or frequent cold sufferers” aged 7-49 given 9,000-40,000 IU A, 120,000-300,000 IU D, or both, daily Sept-June for three years. Spiesman IG. Massive does of vitamins A and D in the prevention of the common cold. Arch Otolaryngol.1941;34(4):787-791.

45. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

46. Do Americans Consume Too Much Vitamin A? • Four percent of obese Wisconsin residents have elevated retinyl esters, a sign that the liver’s capacity to store vitamin A is overloaded. • Obesity is associated with fatty liver disease, which compromises vitamin A storage. • Vitamin D mobilizes vitamin A from the liver. Obese people are three times more likely to have low vitamin D status than non-obese people.

47. Most Americans May Consume Too Little Vitamin A • According to the Third National Health and Nutrition Examination survey (NHANES-III), half of all Americans consume less than the RDA for vitamin A and over a quarter consume less than half the RDA. • The RDA for vitamin A is much lower than the amount found in some traditional diets and five times lower than the doses used to lower the risk of infection in controlled trials conducted from 1920-1940.

48. Recent Myths Circulated About the Vitamin A in Cod Liver Oil • Vitamin A Increases Mortality • Vitamin A Increases the Risk of Infection • Vitamin A Causes Birth Defects • Vitamin A Antagonizes Vitamin D • Americans Consume Too Much Vitamin A

49. How Much Cod Liver Oil? • Used ¾ tsp high-vitamin CLO with ¾ tsp butter oil concentrate in children with tooth decay. • Wrote that the butter oil helped him reduce the dose of CLO to one free of toxicity. • Recommended storing CLO in small bottles to minimize exposure to oxygen. “Cod-liver oil can be given in moderate doses without injury and to great advantage. Seldom, however, should a child be given more than a teaspoonful a day for extended periods, because of toxic effects that often develop.” ‒ Letter to Nieces and Nephews

50. John Hughes Bennett, 1841Treatise on Cod Liver Oil • Many peasants would take 1/2-1 pint and repeat 4-8 days until cured. • Medical men would give 2-4 tbsp to adults and 1-3 tsp to children. • Topical use, including drops in the eye when appropriate, can augment internal use. • Long term excessive use of cod liver oil in some patients could lead to: • Gastrointestinal symptoms including atrophy • Itchy skin eruptions • Excessive evaporation from the skin • Excessive menstrual bleeding “It is now also well known that in many cases where the patient has taken it uninterruptedly for six or seven months, nausea, vomiting, loss of appetite, or other derangement of the digestive functions have arisen . . . It has been observed that the digestion has become gradually more and more deranged, and that even atrophy was thus occasioned.”