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Milk, the forgotten antimalarial

May 19, 2014 - 13:30 -- Pierre Lutgen

It all begins in 1952 with the work of the Liverpool School of Tropical Medicine (BG Maegraith et al, British Medical Journal, 1952, 1382-3). They found that in rats inoculated with Plasmodium berghei and living on a diet of milk there was a strong suppression of the growth of the parasites. This was valid for retail whole cow’s milk, reconstituted dried milk from different origins and human milk. Most rats on normal laboratory diet died in a few days. The authors suggested that the milk might contain an inhibitory substance and that herein lies the explanation of the common observation that severe malaria is not often seen in very young infants. In these first experiments only blood-transmitted malaria had been studied.

The London School of Tropical Medicine followed-up on this early work (RS Bray et al., Brit Medical Journal, 1953, 1200-1) and confirmed that sporozoite-induced infections of Plasmodium cynomogi in monkeys behaved much the same as blood-induced infections. But after a return to normal diet a severe recrudescence took place.

At the same time work done by Wilson and Garnham on the shores of lake Victoria suggested that milk might be deficient in certain nutrients required by the parasite, but that these are present in any normal diet. For the first three months in life children are exclusively breast-fed and they stay malaria free. At the third or fourth month mothers usually start giving them a variety of foods in addition to the breastmilk, and these extras might supply the nutrients required by the parasite.

The National Institute for Medical Research (F Hawking et al., British Medical Journal, 1953 1201-2) finds that milks contains very little p-aminobenzoic acid (PABA), not more than 0.004 ppm. This substance is much more plentiful in some of the constituents of a good laboratory diet, where the vegetal components contain up to 60 ppm of PABA. In vitro Plasmodium requires PABA for satisfactory growth. Experiments were undertaken to study this possibility. Rats were maintained on different diets: normal diet, milk, milk with 1000 ppm of PABA. Only the rats on the milk diet stayed free of P. berghei on day 12.

In 1980 the University of Minnesota ( MJ Murray et al., British Medical Journal, 1980 1351-2) showed that milk had a salutary effect on amoebiasis. Milk-drinking African nomads showed an unusual freedom from infection with Entamoeba histolytica compared with similar nomads taking a mixed diet. The authors related this to a low content in iron in cow’s milk. A personal communication from Dr Patrick Ogwang informs that in Uganda malaria is highest in East and North Uganda where the staple food is cereals with high iron content, in western Uganda where milk and low iron foods are eaten most malaria is low. In the past however, people in East and North also kept cows (zebu) and took milk regularly and malaria was not as rampant.

In 1983 a five month study was undertaken in Brazil (JJ Ferraroni, Mem Inst Oswaldo Cruz, 78, 27-35, 1983) to test the effect of a total milk diet on the susceptibility of mice to various doses of a the rodent malaria P berghei. The development of humoral immunity was followed by quantitation of the specific serum immunoglobulins (IgG and IgM). High levels of IgG antibodies persisted for 150 days , IgM antibodies were only observed during the two first weeks of infection. The results indicated that a milk diet administered to mice as the only source of food protected them against fatal malaria infection regardless of the number of parasites inoculated. The acquired immunity was still present in the mice at 150 days post inoculation.

But these very promising treatments were ignored by Bigpharma and subsidized research. Obviously dairy milk or dried milk is not an interesting cash cow in the fight against malaria.

Only more recently, in the light of resistance to most, if not all, of the pharmaceutical molecules (chloroquine, amodiaquine, lumefantrine, chloroquine, sulfadoxine-pyrimethmine) some research groups have tried to better understand these fifty years old findings. And the proposed role for PABA (p-aminobenzoic acid) seems to be confirmed. (GA McConkey, Antimicrob Ag Chemotherapy, 1999, 43-1, 175-177) (W Krteschmar, Z Tropenmed Parasitol 1966,17-4, 375-90). Plasmodium generates it’s own PABA in its apicomplexan organelle, but not in quantities sufficient to guarantee survival and multiplication of trophozoites and schizonts in the infected erythrocyte (GA Kiczka et al., J Infect Dis. 2003, 188, 1776-82). And as the human body does not generate its own PABA or folates, but takes them essentially from green vegetables, the parasite has to rely on this supply. If the diet is exclusively on milk it has no chance to survive.

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Comments

Submitted by modou diop (not verified) on

In the Wall Street Journal of May 20 Melinda Gates said "Many newborn deaths can be prevented by simple, inexpensive measures- such as teaching women to breast-feed, which immediatela gives a baby nutrients and hydration, and guards against infection, one of the biggest killers of newborns.
Each year 2.9 million infants die in their first 28 days of life"

Submitted by marc vanacker (not verified) on

In a WHO study it was found that the treatment success rate with Coartem was increased by 15 % when the treatment was supplemented with milk or fatty food (Trop Med Internat Health, 2006, 11-12, 1800-7)

And Novartis states that it is important to take every dose of Coartem with food or milk, infant formula, pudding...

Wijnberg John's picture
Submitted by Wijnberg John on

Taking coartem with milk improves absorption ..is it the milk or the higher plasma concentrations? not seen any studies on this ...superb article by the way, Thanks.

Submitted by Nayna Patel on

A similar effect has been reported for Dengue, especially the lipid components in goat's milk. This is fascinating and should be added to the arsenal of anti dengue/malaria precautionary measures in a major way.

Submitted by irene teis (not verified) on

Iron is essential for the survival and multiplication of the Plasmodium parasite. But as for humans an excess of iron is poisonous and a lack of iron may lead to fatal anemia. A known hormetic effect.

Several scientific papers have shown that in humans iron deficiency appears to protect against severe malaria while iron supplementation increases risks of infection and disease.

It would thus be advisable to keep the iron concentrations rather on the low side. This can be achieved by drinking milk. Lactoferrin, a glycoprotein found in milk, has the ability to bind Fe ions with high affinity and to regulate iron distribution within the body.

Lactoferrin also stimulates phagocytosis , a mechanism to remove pathogens, by both neutrophils and macrophages in response to infection. Lactoferrin also modulates the expression of pro-inflammatory cytokines ( such as IL-6, IL-8) avoiding an overactive immune response.

Pierre Lutgen's picture
Submitted by Pierre Lutgen on

Among the flavonoids and essential oils present in Artemisia annua alpha-pinene has by far the lowest IC50 against Plasmodium falciparum in vitro (PJ Weathers et al., Industrial Crops and Products, 2014, in press). This is confirmed by a research team at the Teikyo University in Tokyo Ryuichi Fujisaki et al, Mar 2012)

A French INRA study found that the most abundant monoterpenes (essential oils) in milk from cows grazing natural diversified pasture were alpha-pinene, beta-pinene and limonene (G Tornambé et al., J Dairy Sci 2006, 89-6, 2309-19) A paper published by another French research team (E.Serrano et al., J Animal and Feed Sciences, 16,2007. 168-179) shows that muscle, fatty tissues and milk are very rich in alpha- and beta-pinene, not only when the cattle are fed extra doses of essential oils, but also in standard milk.

In human volunteers for alpha-pinene absorbed by inhalation only 0.001% is eliminated by urine .The main part accumulates in adipose tissues and is released progressively into blood (AA Falk et al., Scand J Work Envir Health, 1990, 16, 372-78) Terpene content for milk samples is characterized by the same terpenes as those added to food. The terpenes appear to be transferred unaltered into the milk. Volatile terpenes in essential oils, which could influence milk flavor, are transferred into milk via both gastrointestinal and respiratory exposure. Most of it is probably absorbed by inhalation of pinenes emitted by plants or trees. Among all monoterpenes emitted by trees alpha-pinene has on the average the highest percentage (Sophie Moukthar, Thèse de doctorat, 205, Institut Polytechnique de Toulouse). Primary agents of the tree's defense are monoterpenes, aromatic molecules such as pinenes.

Pinenes and limonene from Artemisia.arborescens also display antiviral properties by inactivating viruses and inhibiting cell-to-cell diffusion (Barbara Adorjan, Diplomarbeit, Universität Wien). They increase the activity of human natural killer cells (Q Li et al., J Biol Regul Homeost Agents, 2010, 24, 157-65). The Japanese call it a forest bathing trip. Pinenes have strong antimicrobial properties (AM Leite et al., Rev Bras de Ciencias Farmaceuticas, 43, 2007). These molecules also have immunostimulating, anti-inflammatory and gastroprotective properties (DK Lima et al., J Ethnopharmacology), 142, 2012, 274-282).

 

No wonder that mother’s milk does wonders.