Cod Liver Oil

Our Number One Superfood!

Regional Wise Traditions

September 2013, Portland, OR

Chris Masterjohn, PhDThe 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.

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."

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 . . .”

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.

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 Hospital for Consumption and Diseases of the Chest, presented to the Committee of

Management by the Physicians of the Institution. J Churchill, 1849, pp. 31-41.

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

Report of the Commissioner for Fish and Fisheries, 1894, 1902.

Did Cod Liver Oil Contribute to the Eradication of Tuberculosis Mortality?

Thomas McKeown, The Modern Rise of Population, 1976.

Use of CLO as a Treatment

Similar Decline in Tuberculosis Mortality in the United States

Death rateper 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.

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.

Dogs Fed Vitamin A-Deficient Diets Developed Pneumonia

Butter (A)

Olive Oil

Cod Liver Oil (A+D)

Soft bones, partially collapsed lungs, bronchial pneumonia.

Soft bones, partially collapsed lungs, free of infection.

Well mineralized bones, fully functioning lungs, free of infection.

Green HN, Mellanby E. Vitamin A as an Anti-Infective Agent. BMJ. 1928;2:691-6.

Vitamin A, Not Vitamin D, Protected Against Infection in Rats

Vitamin-Deficient Diet(Heated Casein, Rice Starch, Sugar, Olive Oil, Lemon Juice, Mineral Salts)

Diet Plus Vitamin D2

Diet Plus D2 and Vitamin A(Dried Cabbage, Butter, or Cod Liver Oil)

Diet Plus Vitamin A

Infection(tongue, throat, eyes, lungs, GI tract)

Hastened onset of infection

No Infection

No Infection

Green HN, Mellanby E. Vitamin A as an Anti-Infective Agent. BMJ. 1928;2:691-6.

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.

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.

Cod Liver Oil Concentrate Reduces Measles Mortality Over Half

Ellison JB. Intensive Vitamin Therapy in Measles. BMJ. 1932;2:708-11.

Measles Mortality (% of Cases Resulting in Fatality)0123456789

10

Control

Cod Liver Oil Concentrate

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

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.

Did Cod Liver Oil Contribute to the Eradication of Tuberculosis Mortality?

Thomas McKeown, The Modern Rise of Population, 1976.

Use of CLO as a Treatment

Identification of Fat-SolubleVitamins

Vitamin A as “Anti-Infective”

Thomas McKeown, The Modern Rise of Population, 1976.

Did Cod Liver Oil Contribute to the Eradication of Measles Mortality?

Identification of Fat-Soluble Vitamins

Vitamin A as “Anti-Infective”

Did Cod Liver Oil Contribute to the Eradication of Measles Mortality?

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.

IdentificationOf Fat-Soluble

Vitamins Vitamin A as“Anti-Infective”

Two Worlds Collide: Antibiotics Replace Interest in Cod Liver Oil

University of Wisconsin, Madison Heinrich Himmler, head of all Nazi police and security forces, touring an IG Farben facility

Vitamin A

Prontosil

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.

Time Magazine – July 15, 1946“Hardier 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.”

“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.”

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

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

Does Vitamin A Increase Mortality?

Over 240 pages

Only two studies on vitamin A as a single treatment

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).

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.

% of Subjects Still Alive After 4.5 Years0

102030405060708090

100

Placebo

25,000 IU Vitamin A

First Study: No Effect on Mortality

Second Study Showed the Number One Cause of Death is…

% Elderly Nursing Home Residents Who...0

102030405060708090

100

Placebo

One Dose of 200,000 IU vitamin A

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.

Second Study Showed the Number One Cause of Death is Getting Old!

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

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.

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

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.

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.

Multivitamins and fortified breakfast cereals?

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.

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.

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.

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).

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

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.

Low Serum Ca2+ Increases PTH, Leading to Bone Resorption

The 25(OH)D Level that Maximally Suppresses PTH Is Considered Optimal

Chapuy et al. Osteoporosis Int. 1997;439-443.

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

Vitamin A Does Not Increase Bone Resorption

PlaceboAD/A+D

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.

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.

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

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.

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.

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

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

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.

“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.”

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

Cod Liver Oil is Rich in EPA and DHA, but not in AA

EPA Selectively Inhibits COX-1 and Inhibits AA Metabolism

Wada M, DeLong CJ, Hong YH. Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem. 2007;282(31):22254-66.

COX-1

COX-2

COX-1 Inhibition Produces Digestive Disorders

More than four out of ten users of NSAIDs (COX-1 and COX-2 inhibitors), especially COX-1 inhibitors, experience digestive symptoms.

Most common symptoms include heartburn, acid reflux, stomach burning, nausea, and bloating. One out of four are “a great deal” or “enormously bothered.”

In rats, COX inhibition produces food intolerance and villous atrophy.

Thiefin G, Rene-Marc F, Schaeverbecke T, Soufflet C, Barthelemy P. Characteristtics and Impact of Upper GI Symptoms in Patients Treated With NSAIDs: Results of a Cross Sectional EpidemiologicalStudy in Primary Care. Gasteroenterol. 2008;134(4):Suppl1:A7354-5.Pecquet S, Priloult G, Campbell J, German B, Turini M. Commonly Used Drugs Impair Oral Tolerance in Mice. Ann NY Acad Sci. 2004; 1029: 374-378.

Arachidonic Acid Deficiency Leads to Red, Swollen, Scaly Skin

Essential fatty acid

deficiency cured by: Lard – 0.44% PUFA Liver – 0.12% PUFA Methyl linoleate – 1% Methyl arachidonate

– 0.33%

Burr GO, Burr MM. A New Deficiency Disease Produced by the Rigid Exclusion of Fat From the Diet. J Biol Chem. 1929;LXXXII(2):345-67.

Turpeinen O. Further Studies on the Unsaturated Fatty Acids Essential in Nutrition. J Nutr. 1938;15(4):351-66.

Interfering With Arachidonic Acid Metabolism Causes Food Intolerances

Control Egg White COX Inhibitor Egg White and

COX Inhibitor

Villous Atrophy

Newberry et al.Cyclooxygenase-2-dependentarachidonic acid metabolites areessential modulators of theintestinal immune response todietary antigen. Nat Med.1999;5:900-906.

Interfering With Arachidonic Acid Metabolism Causes Food Intolerances

Control

Gluten COX Inhibitor

Gluten +COX Inhibitor

Villous Atrophy

D’Arienzo, et al. A deregulated immune response to gliadin causes a decreased villus height in DQ8 transgenic mice. Eur J Immunol. 2009;39:3552-61.

Interfering With Arachidonic Acid Metabolism Worsens Autoimmunity

ControlCox InhibitorChan and Moore. Resolution of Inflammation in Murine Autoimmune Arthritis Is Disrupted by Cyclooxygenase-2 Inhibition and Restored by Prostaglandin E2-Mediated Lipoxin A4 Production. J Immunol. 2010;184(11):6418-6426.

Two Months After the Induction of Autoimmune Arthritis

COX Inhibitors Attenuate Initiation But Prevent Resolution

Chan and Moore. Resolution of Inflammation in Murine Autoimmune Arthritis Is Disrupted by Cyclooxygenase-2 Inhibition and Restored by Prostaglandin E2-Mediated Lipoxin A4 Production. J Immunol. 2010;184(11):6418-6426.

COX Inhibitor

Control

With Optimal Diet, EPA is Converted to DHA

Diet should: Be rich in minerals, biotin, and vitamin B6.

Be low in polyunsaturated oils and sugar. Be free of heated, rancid oils. Contain EPA in only modest or small amounts. Be rich in sources of AA, such as egg yolks,

liver, and other animal fats.

John Hughes Bennett, 1841Treatise on Cod Liver Oil

“A fat animal diet supports the action of

the oil.”

Cod Liver Oil –Our Number One Superfood

Thank You!