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Diabetes, obesity and malaria: synergy or antagonism

December 24, 2016 - 17:28 -- Pierre Lutgen

Sugar feeding is a fundamental characteristic of mosquito life. It is the basic food of adult mosquitoes, as floral nectar or honeydew. It is the only nutrient consumed by males and probably the more common one for females, even if they need vertebrate blood to produce eggs. Malaria parasites also are dependent on glucose as a nutrient source. As Plasmodium has no capacity to store energy in the form of glycogen they rely entirely on an exogenous supply of glucose. The infected erythrocyte exhibits a substantial increase in its permeability to low molecular weight sugar. The metabolism of the parasite utilizes up to 75 times more glucose than uninfected erythrocytes. Glucose is vital for Plasmodium. An in vitro study has shown that growth and proliferation is impaired at low blood sugar levels.

           H Humeida G Pradel A Stich M B Krawinkel. The effect of glucose and insulin on in vitro proliferation of Plasmodium falciparum Journal of Diabetology 2011 3 6 2011

Low glucose levels can be achieved through fasting or ketosis and it appears that this will ward off malaria. Malaria apparently recurs in famine victims as a result of refeeding.

           Anuraj Shankar, “Malaria and Nutrition”, 229f. in Nutrition and Health in Developing Countries, Richard D. Semba, Martin W. Bloem eds.

Hypoglycemia is a common clinical problem in neonates, where 10 percent at least have difficulties in maintaining a plasma glucose level above 1.7 mM, (30 mg/dL) and this may protect them against malaria. is less common in infants and toddlers, and is rare in older children. In children < 6 years the blood glucose is on the average 8.3 mM ( 150 mg/ dL), reaches in fact a maximum at 5-6 years, and above that age stabilizes around 6.1 mM. Concentrations above 11.0 mM are considered as overt hyperglycaemia. The normoglycemic range of healthy individuals the range is 3.0 – 7.0 mM. The threshold below which parasite proliferation is impaired falls well in the range of normal blood glucose levels in vivo. It is very common that after a night of fasting levels of 3mM are reached. This low level can be rapidly reverted by the ingestion of glucose: 75 gr for example increase the plasma concentrations after one hour from 5.2 mM to 7.1 mM to fall back at 5.2 mM after 3 hours.

Estimating individual exposure to malaria in the field on a cohort of 2425 children and young adults it was found that probability of infection is highest at 5 years drops at 10 years and further at 20 years There is a striking parallelism with blood glucose levels in the previous paragraph.

            Ally Olotu, Gregory Fegan, Juliana Wambua, Estimating Individual Exposure to Malaria Using Local Prevalence of Malaria Infection in the Field PLOS March 29, 2012 http://dx.doi.org/10.1371/journal.pone.0032929

Gastric and small intestine permeability for sucrose is increased in malaria patients.

             Wilairatana P, Looareesuwan S, Meddings J, Ho M, Sutherland L. Increased gastrointestinal permeability in falciparum malaria. Clinical Infectious Diseases 1997; 24: 430-435.

There is evidence that this higher glucose level increases the attractiveness for Anopheles feeding. This has been demonstrated for pregnant women where the number of mosquitoes approaching the patient each night is 1.7-4.5 times higher probably because they have a higher glucose level.

              J. Ansell, K.A. Hamilton, M. Pinder, G.E.L. Walraven and S.W. Lindsay, Short-range attractiveness of pregnant women to Anopheles gambiae mosquitoes. Trans R Soc Trop Med Hyg 96:2, 2002, 113-116.

The biting rates were found to 0.94 bites/woman-night for pregnant women versus 0.49 for non-pregnant. The consumption of soft drinks and beer in the evening also sharply increases human attractiveness to malaria mosquitoes. The ingested carbohydrates provide a highly nutritious blood-meal and probably the adhesion of Plasmodium falciparum parasites.

              Lefèvre T, Gouagna LC, Dabiré KR, Elguero E, Fontenille D, Renaud F, Costantini C, Thomas F Beer consumption increases human attractiveness to malaria mosquitoes. PLoS One. 2010 Mar 4;5(3):e9546. doi: 10.1371/journal.pone.0009546.

               Suseela Srinivasan, Michael Yeh, Eric C. Danziger, Melissa E. Hatley, Glucose Regulates Monocyte Adhesion Through Endothelial Production of Interleukin-8. Circulation Research, 92, 2003, 371-377) 

All Artemisia species seem to have a hypoglycemic effect. Treatment of rats with Artemisia annua aqueous extract reduced the serum glucose after 4 weeks from 110 to 70 mg/mL.

             Mojarad T.B., Roghani M., Zare N. effect of subchronic administration of aqueous Artemisia annua extract on α1- adrenoceptor agonist-induced contraction of isolated aorta in rat. Iran. Biochem. J. 2005;

In South Africa Artemisia afra is extensively used for several diseases including diabetes.

           Idris Ahmed Issa and Mohammed Hussen Bule . Hypoglycemic Effect of Aqueous and Methanolic Extract of Artemisia afra on Alloxan Induced Diabetic Swiss Albino Mice. Evid Based Complement Alternat Med. 2015; 2015: 752486

Methanol extracts of A. absinthium have a strong hypoglycemic and hepatoprotective activity.

           Goud, B.J. (2011), “Methanol extracts of A. absinthium have a strong hypoglycemic and hepatoprotective activity”, Int J Adv Pharmac Res, 2, 7.

For A. herba alba the ethanol-water extract produced stronger hypoglycemic effect than the hexane extract.

           Nagwa E.Awad, Ahmed A. Seida, Zakaria El-Khayat Nermeen Shaffie and Ahmed M. Abd El-AzizJ Hypoglycemic Activity of Artemisia herba-alba (Asso.) used in Egyptian Traditional Medicine as Hypoglycemic Remedy. Appl Pharmac Sc. 02:03, 2012, 30-39).

A. sieberi has been studied for a similar effect in Iran.

           A Allali, H Benmehdi. Phytotherapy of Diabetes in West Algeria. Asian Journal of Chemistry Vol. 20, No. 4 (2008), 2701-2710

           Al-Kazraji SM, al-Shamaony LA, Twaij HA, Hypoglycemic effect of Artemisia herba alba. J Ethnopharmacol 1993 40(3) 163-6

           Al-Waili, Treatment of diabetes mellitus by Artemisia heba alba extract. Clin Exp Pharmacol Physiol 1986, 13(7) 569-73

For A. herba alba the ethanol-water extract produced stronger hypoglycemic effect than the hexane extract

          Nagwa E.Awad, Ahmed A. Seida, Zakaria El-Khayat Nermeen Shaffie and Ahmed M. Abd El-AzizJ Hypoglycemic Activity of Artemisia herba-alba (Asso.) used in Egyptian Traditional Medicine asHypoglycemic Remedy. Appl Pharmac Sc. 02:03, 2012, 30-39). A. sieberi has been studied for a similar effect in Iran.

         S Nofal, S Mahmoud, R Fawzy Antidiabetic effect of Artemisia judaica extracts. Res J Med Med Sc 2009, 4(1), 42-48

          K Mansi, M Amneh. H Nasr.  The hypolipidemic effects of Artemisia sieberi (herba alba). Internat J Pharmacology. 2007, 3, 487-491

In Mexico Artemisia ludoviciana is used against diabetes

           Anaya-Eugenio GD, Rivero-Cruz I, Rivera-Chávez J1, Mata. Hypoglycemic properties of some preparations and compounds from Artemisia ludoviciana Nutt. J Ethnopharmacol. 2014 Aug 8;155(1):416-25. doi: 10.1016/j.jep.2014.05.051.

US Patent 6350478 B1 2002 describes a process for preparing fractions of Artemisia judaica which are effective against diabetes in mammals.

Artemisia dracunculus (tarragon) however has little antidiabetic effect.

           Swanston.Flat SK, Day C. Evaluation of traditional plant treatment for diabetes. Acta Diabetol Lat 1989 26(1), 51-5

Remains the question which constituents of artemisia herbs cause this hypoglycemic effect.

Only minor effects have been detected for essential oils, quercetin, rutin, ellagic acid. Polyphenols and essential oils only have a minor impact and their role is controversial.

           Silvy Mathew, S. John Britto, In vitro antidiabetic Activity of Nerolidol: An Active Compound Isolated From Alpinia Calcarata IJSR, Volume 3 Issue 6, June 2014 ISSN (Online): 2319-7064

Polysaccharides seem to have a minor effect. They inhibit the intestinal absorption of glucose.

            Fei Wang Research, Progress on Polysaccharides Hypoglycemic Mechanism and Therapeutic Potentialoll of Chem & Life Sci. Maoming China 9: 57-62.

                                                                                      The contribution of condensed tannins

The fact that mostly aqueous or ethanolic extracts have an antidiabetic impact points to polar rather than to lipohilic constituents of the Artemisia plants. Recent publications confirm this hypothesis and the major apolar contribution stems from proanthocyanidins (condensed tannins).

             Gonzalez-Abuin N, Binent M, Casanova-Marti A, Procyanidins and their healthy protective effects against type 2 diabetes.. Curr Med Chem 2015, 22(1), 39-50

Plants rich in proanthocyanidins like neem, cinnamon, grape seed or peel, sorghum, pomegranate peel, apple with peel, blueberry all have a strong antidiabetic effect.

             Anunciaçao PC, Cardoso LM, Queiroz, Consumption of a drink containing extruded sorghum reduces gylcaemic response of the subsequent meal. Eur J Nutr 2016 oct 12 

             Inent M, Blay M, Bladé MC, Ardevol A, Grape seed-derived procyanidins have an antihyperglycaemic effect. Endocrinology2004, 145 (11), 4985-90

             I Khan, Safdar M, Ali Khan MM, Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes 2003, 26,12, 3215-8

             Bharat Pokrel, Sagar Rijal, Ankit Pandeya. Investigations of antioxidant and antibacterial activity of leaf extracts of Azadirachta indica, Afric J Biotechnology2015, 14(46) 3159-3163

Artemisia plants are also rich in proanthocyanidins. A very recent paper deals with Artemisia herba alba and finds a concentration of 2 100 mg/100g.

            Laouini S Eddine, Ouahrani M Redha, Segni Ladjel. Influence of solvent extraction on phenolic content, antioxidant and anti-inflammatory activities of aerial parts extract from Algerian Artemisia Herba-alba. J Pharmacy Res, 2016, 10, 58-64.

Another paper detected the presence of anthocyanidins and tannins in several Artemisia species in Iran without quantifying them: A.absinthium, A.annua, A.biennis, A.diffusa, A santolina, A turanica, A.vulgaris, A. sieberi.

            Mehdi Mojarab, Seyyed Ahmad Emami, Mohammad Hassanzadeh-Khayyat. Antioxidant activity of methanol extracts of different species of Artemisia from Iran. Pharmacologyonline 2: 797-807 (2009)

A more recent paper from Iran finds 340 mg/100 g in Artemisia annua leaves and only 30 mg/100g in stems,

            Mazandarani, M.; Majidi, Z.; Zarghami-Moghaddam, P.; Abrodi, M.; Hemati, H.; Fathiazad, F Essential oil composition, total phenol, flavonoid, anthocyanin and antioxidant activities in different parts of Artemisia annua L. in two localities (North of Iran). Journal of Medicinal Plants and By-Products 2012 Vol.1 No.1 pp.13-21 ref.50

            K Ghazanfar, BA Ganai, S Akber, K Mubashir, Antidiabetic activity of Artemisia amygdalina In streptomycin induced diabetic rats. Biomed Res Interna, 2014 ID 185676

A large cohort study shows that a greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk. This confirms the proanthocyanidin hypothesis. Grape skins are rich in proanthocyanidins and the latter are absent in grape juice.

           Isao Muraki, Fumiaki Imamura Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies BMJ 2013;347:f5001 doi: 10.1136/bmj.f5001 

                                                                                                        The contribution of arginine

Experiments conducted by researchers from the University of Copenhagen show that the amino acid arginine – found in a wide variety of foods such as salmon, eggs and nuts – greatly improves the body’s ability to metabolize glucose. Arginine stimulates a hormone linked to the treatment of type 2 diabetes, and works just as well as several established drugs on the market.

              Christoffer Clemmensen, Sanela Smajilovic, Eric P. Smith, Stephen C. Woods, Hans Bräuner-Osborne, Randy J. Seeley, David A. D'Alessio, and Karen K. Ryan Oral l-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice. Endocrinology. 2013 Nov; 154(11): 3978–3983.

In fact, already in 1966 the University of Michigan had found that the intravenous administration of amino-acids to healthy subjects, either as mixtures or individually, stimulated the release of insulin.

               Floyd, JC, Jr., SS Fajans, JW Conn, et al., Stimulation of insulin secretionby amino acids. J Clin Invest. 1966; 45 (9): 1487-1501.

The most effective stimulus was by arginine given alone. In 1998 a study from India showed that the action of arginine is related to the production of nitric oxide.

              I Krishna Mohan and UN Das, Effect of L-Arginine.Nitric oxide on chemical induced diabetes mellitus. Free Radical Biology & medicine, 1998, 7, 757-765

A recent study from Ukraine has analyzed the amino acid content in some 8 plants of this subgenus and found that they are all 5 to 10 times richer in arginine than other herbs or vegetables, with A annua top-ranking (2 g/100g).

             Ochkur O. AM Kovaleva, Amino acids composition of subgenus Artemisia herbs. Chemistry of Natural Compounds2013, 49-3, 589-591

Lifestyle strategies including diets rich in nitrite and nitrate along with moderate physical exercise, which promotes NO production, may be the best approach for management of diabetes through restoration of NO homeostasis. The plasma concentration of NO is significantly lower in both hypertensive patients and diabetic patients.

             Shiekh GA, Taha A, Saquib NK, Rubiya D, Khurshid IA (2011) Reduced nitrate level in individuals with hypertension and diabetes. J Cardiovasc Dis Res 2: 172–176. doi: 10.4103/0975-3583.85264.

            Paolo T, Diego C, Alessandra C, Monica V, Anna C, et al. (2010) Nitric oxide synthesis is reduced in subjects with type 2 diabetes and nephropathy. Diabetes 59: 2152–2159. doi: 10.2337/db09-1772.

Recent evidence suggests that the supposedly inert anions nitrate and nitrite are metabolized in blood and tissues to form nitric oxide NO and other bioactive nitrogen oxides. These stimulate pancreatic Langerhans islet function and subsequent insulin formation in vivo

            Nyström T, Ortsäter H, Huang Z, Zhang F, Larsen FJ, Weitzberg E, Lundberg JO, Sjöholm Å. Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion. Free Radic Biol Med. 2012 Sep 1;53(5):1017-23. doi: 10.1016/j.freeradbiomed.2012.06.031.

It seems that dietary nitrate/nitrite could be a compensatory fuel for a disrupted nitrate/nitrite/NO pathway and related disorders in diabetes.

           Ghasemi A, Zahediasl S. Potential Therapeutic Effects of Nitrate/Nitrite and Type 2 Diabetes Mellitus. Int J Endocrinol Metab. 2013;11(2):63-4. DOI:5812/ijem.9103

           Zahra Bahadoran, Asghar Ghasemi, Parvin Mirmiran, Fereidoun Azizi and Farzad Hadaegh.Beneficial effects of inorganic nitrate/nitrite in type 2 diabetes and its complications Nutrition & Metabolism 2015 12:16 DOI: 10.1186/s12986-015-0013-6

           Jon O. Lundberg, Mattias Carlström, Filip J. Larsen, Eddie Weitzberg. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovascular Research. DOI: http://dx.doi.org/10.1093/cvr/cvq325

This of course is in complete contradiction of the WHO guidelines of 50mg/L for nitrate.

            World Health Organization. Guidelines for drinking water quality. Second addendum to third edition, Geneva 2008.

A British systematic review and meta-analysis

           Patrice Carter, Laura J Gray, Jacqui Troughton,, Melanie J Davies Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c4229

demonstrated that a diet rich in green, leafy vegetables, but not fruit and other vegetables may confer protection against the risk of developing type 2 diabetes mellitus. This is definitely the case for some medicinal herbs like Artemisia annua or Artemisia maritima which are very rich in nitrates and arginine.

                                                                                                       Does diabetes have antimalarial properties?

A thesis from Sudan presents troubling facts.

              Hassan Humeida. Der Verlauf von Malaria bei Patienten mit Diabetes mellitus in Afrika - Feldforschungen im Zentral-Sudan - Dissertation. Giessen, Februar 2011

Comparing a cohort B of 126 people with malaria alone vs. a cohort A of 64 people with diabetes and malaria they find a lower parasitemia in group A, much less glucose in group B, much less secondary effects and less malaria symptoms in group A. The duration of malaria is much longer in group B. Insulin has no influence. It is well known that G6PD deficiency protects against malaria. High glucose impairs G6PD activity.

              Zhang Z , Liew CW, Handy DE, Zhang Y, Leopold JA, Hu J, Guo L, Kulkarni RN, Loscalzo J, Stanton RC. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis. FASEB J. 2010 May;24(5):1497-505. doi: 10.1096/fj.09-136572.

Hyperglycaemia can reduce expression of the G6PD gene and activity of the enzyme. In a large cohort study among 940,085 individuals, 52,371 had G6PD deficiency. A significantly higher proportion of patients with G6PD deficiency was found among the diabetic population aged 45–64 years

              Anthony D. Heymann,, Yossi Cohen, and Gabriel Chodick , Glucose-6-Phosphate Dehydrogenase Deficiency and Type 2 Diabetes. Diabetes Care 2012 Aug; 35(8): e58-e58.

              Carette C, Dubois-Laforgue D, Gautier JF, Timsit J. Diabetes mellitus and glucose-6-phosphate dehydrogenase deficiency: from one crisis to another. Diabetes Metab. 2011 Feb;37(1):79-82. doi: 10.1016/j.diabet.2010.09.004.

              LP Stabile, SA Klautky, M Minor, LM Salati. Polyunsaturated faty acids inhibit the expression G6PD gene in hepatocytes. J of Lipid Research 1998 39 1951-1963

              Z Zhang, Chong Wee Liew, Robert C Stanton, High glucose inhibits G6PD leading to increased oxidativer stress. FASEB J. 2009, 24-5, 1497-1505

There is a growing body of evidence that glucose ingestion causes a number of pro-inflammatory changes in normal as well as diabetic humans. Glucose stimulates the endothelial production of the pro-inflammatory Interleukin-8. And if Artemisia reduces glucose in blood, it will at the same type reduce these inflammatory processes, improve liver and renal functions and give a sense of wellbeing as it was noticed in some trials in Senegal and in South Africa.

               Anthony Jide Afolayan and Taofik Olatunde Sunmonmu. Artemisia afra Jacq. Ameliorates Oxidative Stress in the Pancreas of Streptozotocin-Induced Diabetic Wistar Rats. Bioscience, Biotechnology, and Biochemistry Vol. 75 , Iss. 11,2011

Diabetes mellitus is characterized by hyperglycemia., an abnormal elevation of the blood glucose level. Hyperglycemia generates oxygen free radicals, advanced glycated end products, ROS and inhibits glutathione GSH. This is exactly what the Plasmodium parasite tries to avoid and even to counteract. Hyperglycemia would does have an action similar to that of many antimalarial drugs which attack the parasite by the same oxidative mechanism.

            Aljada et al. Glucose ingestion induces an increase in intranuclear nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy human subjects. Metab Clin Exp 55:1177-85 (2006)

The H₂O₂ concentration has been found to be four times higher in type 2 diabetes. These results are similar to those found in a study that showed an increased mitochondrial H₂O₂ production in hyperglycemic mice

            Msolly A, Abdelheidi M, Kassab A. Hydrogen.Peroxide: an Oxidant Stress Indicator in Type 2 Diabetes Mellitus. JCvD 2013;1(2):48-52.

Under hyperglycemic conditions glucose is metabolized into aldehydes which via autoxidation generate hydrogen peroxide and the highly toxic hydroxyl radical *OH¯.

            A Kassab, A Piwowar. Cell oxidant stress delivery and cell dysfunction onset in type 2 diabetes. Biochimie 2012, 94, 1837-1848

Other authors observed both an increase of H₂O₂ production by isolated mitochondria and an increase in xanthine-induced- H₂O₂ production. They find a plasma concentration 2 times higher in diabetic mice.

             Amélie Bravard, Charlotte Bonnard, Annie Durand, Marie-Agnès Chauvin, Roland Favier, Hubert Vidal, Jennifer Rieusset. Inhibition of xanthine oxidase reduces hyperglycemia-induced oxidative stress and improves mitochondrial alterations in skeletal muscle of diabetic mice. American Journal of Physiology - Endocrinology and Metabolism Published 25 February 2011 Vol. 300 no. 3, E581-E59

All in all hydrogen peroxide being a killer of plasmodium, in is logical to expect that malaria would be lower in diabetic patients

Proanthocyanidins are efficient against this oxidative stress, reduce glucose and triglycerides, reduces NFκB and iNOS. But extreme precaution is required not to work with an overdosis of proanthocyanidins.

              T Yokozawa, EJ Cho, CH Park, JH Kim. Protective effect of proanthocyanidin against diabetic oxidative stress. Evidence Based Complementary and Alternative Medicine, 2012, Article ID 623879

Similar precautions need to be taken in the case of malaria infection. During the Sahelian famine in Niger, victims were admitted to the hospital for refeeding and it was observed that Plasmodium falciparum malaria developed in many of these individuals within a few days, often resulting in cerebral pathology. Because there was no transmission of malaria at the hospital it was believed that feeding had provided a essential nutrients for sequestered parasites, leading to recrudescent infection. In another study, famine victims were given either grain or milk for rehabilitation. It was observed that those given grain were more likely to experience recrudescence. The Bengal Famine Commission already in 1945 stated that refeeding tended to precipitate malaria disease in those carrying low-grade infections.

             Murray MJ, Murray AB, Murray NJ, Murray MB. 61. Diet and cerebral malaria: the effect of famine and refeeding. Am J Clin Nutr. 1978 Jan;31(1):57-

In a trial with mice it was found that low protein diets drastically increased the survival after Plasmodium yoelii. More important is the fact that these surviving mice were found to have acquired potent innate immunity.

            Ariyasinghe A, Morshed SR, Mannoor MK, Bakir HY, Kawamura H, Miyaji C, Nagura T, Kawamura T, Watanabe H, Sekikawa H, Abo Protection against malaria due to innate immunity enhanced by low-protein diet. J Parasitol. 2006 Jun;92(3):531-8.

                                                                                                 Is a high fat, ketogenic diet beneficial against malaria.

People living in the poorest countries are the most afflicted by malaria and this may be related to nutrition. Their basic staple is rich in carbohydrates (starch). The main source of energy is thus glucose, but not lipids and ketone bodies. Glucose is food for Plasmodium which needs 60 times more of this fuel than the healthy erythrocyte. Fatty, ketogenic diet will provide less nutrients to the parasite although this has not been explored in depth. Breastfeeding seems to contribute to the immunity of newborns during 6 months and breast milk is rich in fat.

The effect of fatty ketogenic diet might also explain many anecdoctical results on the effect of lipids on Artemisia annua efficiency. In 2009 at the 2d Symposium on Tropical Diseases at Luxembourg, D Rezelman showed that the addition of arachid oil enhanced the efficiency of Artemisia annua extract by a factor 3 in mice. The Brewer Science Library reports that some physicians recommend to take artemisinin with whole milk, cod liver oil, almond oil or flaxseed oil. At the ICEI malaria conference at Roma in April 2010 B Isacchi from the Universitate di Firenze showed that olive extract enhanced the effectiveness of artemisinin. In 2011 clinical trials run by IFBV-BELHERB in Dagana, Senegal showed that a mixture of Artemisia annua leaf powder and peanut butter gave cure rates > 95%. Dr F Roelofsen (personal communication, 2012) showed that when Artemisia annua leaves mixed with 10% fatty yoghurt gave a higher AUC and an extension of half-life for artemisinin from 30 minutes to 2-3 hours. There are several pathways to explain the positive effect of lipids delivered in conjunction with tea. It is possible that an oil rich diet has an effect on the erythrocyte membrane lipid composition, stimulation of calcium channels and permeability.

             A Pagnan, R Corrocher, G Ambrosio. Effects of an olive-oil-rich diet on erythrocyte membrane lipid composition and cation transport systems. Clinical Science (1989) 76, 87-93 87

Lipids may increase the bioavailability of lipophilic substances like artemisinin or essential oils. This effect has been documented for lumefantrine 

            Ashley EA, Stepniewska K, Lindegårdh N, Annerberg A, Kham A, Brockman A, Singhasivanon P, White NJ, Nosten F. How much fat is necessary to optimize lumefantrine oral bioavailability? Trop Med Int Health. 2007 Feb;12(2):195-200.

The positive effect of a ketogenic diet on malaria is known since 60 years. In a trial in India, of 10 rats, 8 weeks old, 5 received a standard diet and 5 a ketogenic diet containing 93% per cent., butter. After a week, all were inoculated with Plasmodium berghei. The number of parasites observed daily and at the peak of infection was much less in the rats given the ketogenic diet.

            S P Ramakrishnan. Studies on Plasmodium berghei Vincke and Lips 1948. 16. Effect of ketogenic diet on the course of blood-induced infection of rats. Indian Journal of Malariology 1954 Vol.8 pp.85-88

More recently this was confirmed in a French paper

             Vincent Robert, Catherine Bourgouin, Delphine Depoix, Catherine Thouvenot, Marie-Noëlle Lombard and Philippe Grellier. Malaria and obesity: obese mice are resistant to cerebral malaria Malaria Journal 2008 7:81 DOI: 10.1186/1475-2875-7-81

PubMed searches with "obesity" and "malaria" yielded 107,545 and 46,653 references respectively. However, association of the two terms produced only 17 entries, indicating that the two communities of researchers occupy distinct scientific niches that do not overlap.. Finally, a search in the French database of all recorded malaria cases (about 45,000) was eloquent: the bodyweight of the studied patients was simply not recorded Current dietary prescriptions by the American Diabetes Association, the American Heart Association, the National Cholesterol Education Program are 30% fat, 60 % carbohydrates. Prior to the advent of exogenous insulin for the treatment of diabetes mellitus in the 1920's, the mainstay of therapy was dietary modification. Diet recommendations in that era were aimed at controlling glycemia (actually, glycosuria) and were dramatically different from current low-fat, high-carbohydrate dietary recommendations for patients with diabetes. For example, the Dr. Elliot Joslin Diabetic Diet in 1923 consisted of "meats, poultry, game, fish, clear soups, gelatin, eggs, butter, olive oil" and contained approximately 5% of energy from carbohydrates, 20% from protein, and 75% from fat. Recent research now finds that low-carbohydrate, ketogenic diet is effective for improving glycemia, reducing obesity and body weight. 

              William S Yancy, Marjorie Foy, Allison M Chalecki, Mary C Vernon and Eric C Westman. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition & Metabolism 2005 2:34 DOI: 10.1186/1743-7075-2-34

A review paper confirms these findings. It revisits the meaning of ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.

                Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2014 May;68(5):641.

 

Diabetes, malaria and diet are fields which needs much more research. Previous prescriptions on low fat diets and low concentrations of nitrate in water not only are obsolete but detrimental.

 

Comments

Submitted by Irene Teis on

This question asked in the blog of Pierre Lutgen “ Diabetes, obesity, malaria: synergy or antagonism” raises a lot of concerns.

A very recent paper from Nigeria confirms the thesis of the University of Giessen describing large scale assessments in Sudan: malaria takes a more difficult course in diabetes patients than in healthy individuals. In Nigeria the malaria parasite load (number/µl of blood) was 2943 for non-diabetics, but only 2376 for diabetics. The fasting blood glucose (mmol/L) was 3.89 in non-diabetics and 6.96 in diabetics. Analysis of liver health parameters showed that there was no significant difference for albumin, ALAT, ASAT, bilirubin, except maybe for alkaline phosphatase.

          Ndiok E O, Ohimain E I, Izah S C. Incidence of Malaria in Type 2 Diabetic Patients and the Effect on the Liver. Journal of Mosquito Research 2016. Vol 6 No 15, 1-8

In fact there are less recent papers from Nigeria describing the same beneficial effect of diabetes on malaria. 100 subjects were involved in the trials at an age between 40 and 70, years. The mean parasitic count of the diabetics with malaria was significantly lower than for non-diabetics (103.9 vs 164.4 count/mL). The liver function profile was not significantly different.

           EJ Ikekhazu, EE Neboh, MW Nwobodo. Type-2 Diabetes Mellitus and Malaria Parasitemia: Effect on Liver Function Tests. Asian J Med Sc, 2010 214-217

A more ancient study from India finds that in 76 malaria infected diabetics fever is absent in 16 cases and only in 2 cases for the 72 non-diabetics. The parasite count was 4560 in the non-diabetics and 2058 in the diabetics

           M K Mohapatra, Profile of Severe Falciparum Malaria in Diabetics. Int J Diab Dev Countries, 2001, vol 21, 156.161

This confirms a study from 1995 on streptozotocin induced diabetic mice. They were less anaemic, exerted a significant control of parasitemia and showed enhanced phagocytic activity compared with normal mice. The mice were infected with 3 different types of parasites: Plasmodium berghei, yoelii and chabaudi. In some cases, parasitemia was up to 90% lower in the first 7-10 days of the infection for the diabetic mice.

           K.Elased, JB de Souza, JH Playfair. Blood-stage malaria infection in diabetic mice. Clin Exp Immunol 1995 99, 440-444.

If the administration of antidiabetic drugs in malaria patients does indeed have deleterious effects on the outcome of the malaria infection, this really deserves more studies.

It is disturbing that this information is available in the scientific literature since decades, but ignored by WHO, by pharmaceutical and by medical authorities.