Cornelis de Langen: Diet-Heart Theory, 1916

Cornelis de Langen’s great adventure began in May of 1914 when his ship left Rotterdam for the Dutch East Indies and sailed through the gunmetal-gray waters of the North Atlantic. By a route we cannot document but that likely took him through the Suez Canal, his ship would have steamed through the murky green Indian Ocean and the Strait of Sudah, past Rakita, the tiny islet remnant of Krakatua’s grand explosion, and finally docked, after weeks at sea, in the bustling tropical port of Batavia (the Dutch colonial name for current-day Jakarta).

As Chef de Clinique in Internal Medicine at Groningen University, de Langen had a promising academic career interrupted by this urgent government assignment to the colonies. The young physician, guided by his Groningen chief and mentor, Albert Abraham Hijmans van den Bergh, was well prepared, however, to serve his government, to help the Javanese combat epidemic plague, and to teach internal medicine to the local medical trainees.

Van den Bergh, one of several Jewish physicians who headed departments of medicine in Dutch hospitals, was a portrait of the complete internist: intellectually curious, skilled in the biochemistry of disease, devoted to his patients, and honoring a firm tradition of professional duty. House Officer de Langen practiced and taught in this tradition. The request of his government to serve in the colonies could only be met with dutiful acceptance. Thus, he departed his homeland for an indefinite stay in a world that would prove to be foreign not only in climate, culture, and language, but in the medical profile of its population.

Supported in Batavia by the Foundation for the Education of Indonesian Doctors (STOVIA), de Langen soon established order in the clinic, with its clean-swept yards and pleasant semi-tropical surroundings. His family biographers recount how, with a color-coded chart of ward beds, he could identify at a glance not only the patient and the diagnosis, but the stage of hospitalization and therapy, allowing him to make rounds efficiently and effectively (de Langen and de Langen 1999, 123-128).

International medical academician, Isidore Snapper, one of de Langen’s closest lifetime colleagues, corroborated others’ impressions of the young doctor’s suitability for the job, calling de Langen “a young man with a very original mind,” and writing in his memoirs, “I have always considered de Langen as an excellent example of the inspiration which Hijmans van den Bergh instilled into his pupils” (van Lieburg 2004, 85-86).

Cultural Comparisons: Dutch and Javanese

It was not long before de Langen noted that his native Javanese patients rarely manifested the internal diseases with which he had been accustomed to dealing in Europe. Pursuing this clinical impression, he reviewed ten years of admissions charts and found only five cases of acute gall bladder disease among many thousands of patients passing through the medical wards, and only one on the surgery service out of 70,000 admissions surveyed (de Langen 1999, 130).

After thus documenting the rarity of gallstones, de Langen wrote about his observations of vascular phenomena: “. . . thrombosis and emboli, so serious in Europe, are most exceptional here. This is not only true of internal medicine, but also on surgery, where the surgeon needs take no thought of these dreaded possibilities among his native patients. Out of 160 major laparotomies and 5,578 deliveries in the wards, not a single case of thrombosis or embolism was seen” (de Langen and Lichtenstein 1936, 491-492).

De Langen made similar observations on the absence of angina pectoris and the by-then-recognized syndrome of myocardial infarction. In contrast, his Dutch colonial patients had the frequency of such conditions expected among his fellow countrymen at home. The following confirmatory account is from the memoir of Isidore Snapper:

My friend and former co-resident in Groningen, C. D. de Langen, had discovered in 1916 in Indonesia, that the obligatory vegetarian Oriental, whose intake of cholesterol was practically zero, does not develop gallstones. Soon it appeared that not only cholesterol stones of the gall bladder but also arteriosclerosis and phlebitis (also lung emboli) hardly ever occur among the Orientals (van Lieburg 2004, 171).

De Langen himself confirmed the rarity of coronary syndromes in a report to the Second Conference of the International Society of Geographic Pathology. There he described his survey finding of only one case of angina pectoris among Javanese and six among Chinese admitted in a five-year period to the 500-bed Batavia Municipal Hospital (de Langen 1935).

Outside Hospital

Having thus established rough impressions of comparative CVD prevalence and incidence in the patient population, de Langen proceeded to observe characteristics among defined populations outside the hospital, first comparing the average blood cholesterol level of Javanese, Dutch, French, and Germans, where he demonstrated similarities among the western groups but much lower levels in the Javanese. He also found that Javanese stewards on the Dutch transport lines were metabolically closer to the Europeans than to native Javanese.

In his seminal early paper (published in Dutch), de Langen described clinical relationships among diet, serum cholesterol, and atherosclerosis: “. . . a cholesterol-rich diet and severe metabolic diseases, such as diabetes, obesity, nephritis, and arteriosclerosis, are associated with hypercholesterolemia” (de Langen 1916, 4).

He further connected blood lipids with diet in these early observations: “The question has frequently been asked whether cholesterol concentration of blood and bile is controlled by diet–the diet of the population in the Dutch East Indies differs very much from the Western European diet. The local diet is mainly vegetarian with rice as staple, that is very poor in cholesterol and other lipids” (ibid., 34).

Elsewhere, de Langen reported perhaps the first comment on exceedingly low blood cholesterol values seen in wasting diseases:

The food of the masses which visit our hospitals and polyclinics in Java contains but little cholesterin; the result is a smaller content of cholesterin in the blood. Especially in the very numerous patients with malaria and ancylostomiasis, the cholesterin content is quite often on the very low side. Whenever, in hospitals or elsewhere, we give people a diet rich in lipoids, the quantity of cholesterin in their blood rises at once. (Snapper 1963, 284)

The rice-based, virtually meatless “food of the masses” to which de Langen referred, combined with a pattern of daily activity, added up to a picture of habits and health very different from the European Dutch lifestyle.

From Observation to Experiment

From these observations, de Langen moved logically, comfortably to experimentation. In what was probably the first systematic trial of the effects of diet change on serum cholesterol levels, he found an average 40mg/dl rise in cholesterol in five Javanese natives who were shifted from a rice-based vegetarian cuisine to a six-week regimen high in meat, butter, and egg fats (de Langen 1922, 2-3).

Thus was a cycle completed, from observations on disease frequency, to blood lipid-level differences, to dietary relationships with lipid levels and disease rates, and finally to modification of blood lipid levels by dietary experiment. It seems that, already in the 1920s, de Langen had left to future study in humans only the direct influence on disease risk of diet change and lipid-lowering. But that future would be long in coming.

Perspective on de Langen’s Influence

Did de Langen’s findings, in fact, influence the subsequent pursuit of causal and prevention investigation? His early articles were referenced in other languages, including English and French, but most of what we know about the wake left by his research comes from correspondence with his colleague and fellow Dutchman, Isidore Snapper. Snapper had for a short period taken de Langen’s place as Chef de Clinique at Groningen University Hospital before going on to a notable career at Amsterdam, in China, and in the United States. In 1938, he was posted to head internal medicine at the Peking Medical School, then subsidized by the Rockefeller Foundation. Snapper wrote about how de Langen’s work and correspondence influenced him:

In 1940, I confirmed De Langen’s results . . . by the observation that in North China, coronary disease, cholesterol [gall]stones and thrombosis were practically nonexistent among the poorer classes. They lived on a cereal-vegetable diet consisting of bread baked from yellow corn, millet, soybean flour and vegetables sautéed in peanut and sesame oil. Since cholesterol is present only in animal food, their serum cholesterol content was often in the range of 100 mg. per cent. These findings paralleled the observation of De Langen that coronary artery disease was frequent among Chinese who had emigrated to the Dutch East Indies and followed the high fat diet of the European colonists (Snapper 1963, 284).

It cannot be claimed that de Langen’s remarkable pioneering and multi-disciplined findings, or their powerful implications, actually inundated the medical and nutritional plain of the period leading up to mid-century. They provided at the very least, however, insightful observations, testable hypotheses, background evidence, and intellectual impetus to other investigators who effectively pursued the questions he raised. De Langen’s ideas about cultural differences in lifestyle and cardiovascular risk were, in fact, among the earlier formulations of the diet-lipid-heart disease hypothesis and his studies among its first clinical-epidemiological tests.(1)

It seems unfortunate that de Langen’s early works on diet and disease were not published in English, particularly because, according to Gerson (who made the comment in French), de Langen wrote and spoke “in an elegant English, clear and simple, which made him a classic teacher of first rank” (Gerson 1966, 9). The translation lag time also may have contributed to what Snapper called “historical inaccuracies that necessarily result when a new generation tries to review a concept born half a century previously” (Snapper 1963, 284).

Thus, de Langen did not receive the credit he deserved for his hypotheses or his rigorous testing of them in this early period of modern medicine. But because of the documented influence of his findings on his close colleagues we can trace a direct line–a Dutch Dynasty, if you will–in the drama of diet and chronic diseases, from de Langen in 1916 to Snapper in 1941, to Groen and Keys in the 1950s, and to other Dutch workers up until today.

A symposium to honor the career of Cornelis de Langen was held in Leuven, Belgium, in October of 1999, at which his contributions were gathered together with detailed descriptions of his work by his descendants and successors (Kesteloot and Kromhout 1999, 121-122). (Henry Blackburn)

References

De Langen, C. D. 1916. Cholestrine-stofwisseling en rassenpathologie [CD Cholesterol metabolism and racial pathology]. Geneeskundig Tijdschrift voor Nederlandsch-Indië 56:1-34.

De Langen, C. D. 1922. Het Cholesterinegehalte van het bloed in Indië [Cholesterol content of blood in the Dutch Indies]. Geneeskundig Tijdschrift voor Nederlandsch-Indië 62:1-4.

De Langen, Cornelis D. and A. Lichtenstein. 1936. A clinical textbook of tropical medicine. Amsterdam, Batavia: G. Kolff & Co.

De Langen, E. G. and J. E. de Langen. 1999. C. D. de Langen–his life and work. Acta Cardiologica 54:123-128.

Kesteloot, H., and D. Kromhout. 1999. Cholesterol in a historic perspective.
Report of the Professor C. D. de Langen symposium. The Netherlands, December
4, 1998. Acta Cardiologica 54:121-122.

De Langen, I. 1999. C. D. de Langen and nutrition research. Acta Cardiologica 54:129-133.

Gerson, L. 1966. Le professeur C. D. de Langen. Angéiologie 18:9-12.

Snapper, I. 1963. Diet and atherosclerosis: Truth and fiction. The American
Journal of Cardiology 11 (3):283-289.