European Heart Journal Advance Access published January 9, 2007
Addition of milk prevents vascular protectiveeffects of tea
´lie von Krosigk1, Peter Martus2, Gert Baumann1,
1 Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charite´—Universita¨tsmedizin Berlin, CCM, Charite´platz 1,D-10117 Berlin, Germany and 2 Institut fu
¨r Biometrie und Klinische Epidemiologie, Charite
Received 13 September 2006; revised 28 November 2006; accepted 30 November 2006
Aims Experimental and clinical studies indicate that tea exerts protection against cardiovascular
diseases. However, a question of much debate is whether addition of milk modifies the biological activi-
ties of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the
impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC
Methods and results A total of 16 healthy female volunteers consumed either 500 mL of freshly brewedblack tea, black tea with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD)was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black teasignificantly improved FMD in humans compared with water, whereas addition of milk completely
blunted the effects of tea. To support these findings, similar experiments were performed in isolatedrat aortic rings and endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased theactivity of endothelial nitric oxide synthase by phosphorylation of the enzyme in endothelial cells. Alleffects were completely inhibited by the addition of milk to tea. Of the various kinds of milk proteins,the caseins accounted for these inhibiting effects of milk, probably by formation of complexes with teacatechins.
Conclusion Milk counteracts the favourable health effects of tea on vascular function. This finding
indicates the need for particular awareness in the interpretation and design of studies comprising nutri-tional flavonoids.
flow-mediated dilation (FMD) of human blood vessels is ahallmark of a functional endothelium, with impairment of
Consumption of tea has been inversely associated with
FMD representing an early marker of vascular dysfunction.4,6,7
cardiovascular morbidity and mortality.1 A broad body of
We address the question whether milk affects the
evidence from experimental and clinical studies indicates
beneficial effects of tea on endothelial function. We show
that tea exerts antioxidative, anti-inflammatory, and vasodi-
here that black tea significantly improves endothelial func-
lating effects, thereby rendering protection against cardio-
tion in humans, whereas the addition of milk completely
vascular diseases.2,3 As the worldwide consumption of tea
blunts this amelioration. In our in vitro experiments, we
is second only to water, the beneficial effects of tea rep-
demonstrate that milk caseins account for these inhibiting
resent important public health issues. However, up to now,
it is not known whether addition of milk to tea, as widelypracticed in the UK, influences these vasoprotective proper-ties. We therefore investigated the effects of tea with and
without milk on endothelial function as a sensitive para-
meter of vascular wall homeostasis.4 Many pathophysio-logical
Postmenopausal women were recruited by press advertisements.
characterized by attenuated production of protective
A total of 229 women responded, and interviews were conductedwith these women. Subjects with chronic diseases and known cardi-
vasoactive substances in endothelial cells, resulting in a
ovascular risk factors such as high blood cholesterol, diabetes,
condition known as endothelial dysfunction.5 Undisturbed
arterial hypertension, and obesity as well as with certain food pat-terns (to exclude high regular tea consumption and vegetarian life-style) were excluded. A total of 42 women were invited for clinical
* Corresponding author. Tel: þ49 30 450 513153; fax: þ49 30 450 513932.
examination. All measures of clinical parameters were required to
The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org
be within the normal range to allow study inclusion: lipid profile,
For western blots, cells were treated as described earlier, washed
blood pressure, body mass index, as well as routine internal para-
twice with phosphate buffered saline, and lysed in buffer contain-
meters such as thyroidea-stimulating hormone and sexual steroids.
ing, in mmol/L, HEPES 20 (pH 7.9), NaCl 100, Na3VO4 1, sodium
A total of 16 healthy women (mean age 59.5 + 5) completed the
pyrophosphate 4, EDTA 10, phenylmethylsulfonyl fluoride 1, NaF
study. None of the participants had taken medication for at least
10, okadaic acid 0.1, and 1% Triton X-100. Total protein (15 mg per
3 months before entering the study. The participants were asked
lane) was subjected to sodium dodecylsulfate polyacrylamide gel
to refrain from consuming tea 4 weeks before and during the
electrophoresis, and membranes were probed with anti-phospho-
study. Study subjects were required to make three clinical visits,
eNOS (Ser1179) antibody (1:1000) from Cell Signaling. Bands were
at least 3 days apart and at the same time of day (i.e. 8 a.m.
visualized by using BCIP (5-bromo-4-chloro-3-indolyl phosphate,
after fasting overnight). Each subject consumed 500 mL of boiled
p-toluidine salt) and Nitro Blue Tetrazolium (Sigma).
water, freshly brewed black tea (with 10% water to achieve thesame dilution as tea with milk), or black tea with 10% skimmed
Vasorelaxation studies in isolated rat aortic rings
milk in a crossover study design. Five grams of tea leaves (Darjeelingblack tea, provided by King’s Teagarden, Berlin, Germany) were
Thoracic aortas from male Wistar rats were rapidly excised, cleaned
brewed for 3 min with 500 mL of boiled water. All participants
of connective tissue, and cut into rings 2–3 mm in length for organ-
were required to complete all three visits. FMD and nitro-mediated
chamber experiments. The rings were then mounted on platinum
dilation (NMD) were measured before and 2 h after consumption of
hooks in 10 mL jacketed organ baths containing modified Krebs–
the beverages. The participants had a standardized breakfast (one
Henseleit solution (composition, in mmol/L, NaCl 144, KCl 5.9,
croissant) while they drank the beverage. The study was approved
CaCl2 1.6, MgSO4 1.2, KH2PO4 1.2, NaHCO3 25, and D-glucose 11.1)
´ University Hospital Ethics Committee, and partici-
and 1 mmol/L diclofenac. Tension was gradually adjusted to 2 g
pants provided their written informed consent.
over 1 h. The solution in the bath was maintained at 378C with agas mixture of 5% CO2 and 95% O2. Following equilibration and sub-maximal precontraction with phenylephrine (0.05 mmol/L), relax-
ation to cumulative doses (5–50 mL) of black tea was performed ina volume of 10 mL Krebs–Henseleit solution. Preparation of the
Endothelial function was measured by high-resolution vascular ultra-
various tea beverages was as described earlier, with the exception
sound (Siemens Sonoline Antares), with use of a 13 MHz linear array
that 300 mg/mL of individual milk proteins were used. Selected
transducer. Endothelium-dependent FMD was assessed by measuring
studies were conducted in rings treated with the NOS inhibitor
the change in the brachial artery diameter during reactive hyperaemia
N-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L) before phenyl-
after cuff occlusion of the forearm for 5 min, according to established
ephrine exposure. Vasorelaxation is expressed as percentage of
guidelines.8 The nature of the stimulus and conditions for the measure-
ment of FMD were chosen to obtain a nitric oxide-dependent responseafter a brief period of shear stress in the brachial artery.9,10 Changes in
Concentrations of individual tea compounds
the arterial diameter were measured every 15 s for up to 2 min. FMDwas defined as the maximum percentage change in diameter compared
Tea was prepared as described in study protocols. The concen-
with baseline measurement. Endothelium-independent vasodilation
trations of individual tea substances in brewed tea, in the super-
(NMD) was measured after sublingual application of nitroglycerin
natant of tea with or without addition of 10% milk after
spray (0.4 mg). The increase in diameter of the brachial artery was
centrifugation of the beverage at 13 000 g for 20 min, were deter-
measured from 1–6 min, and NMD was defined as the maximum percen-
mined as described with slight modifications.12 In brief, tea
tage change in diameter compared with baseline measurement.
samples were diluted with 10% acetonitrile containing 500 mg/mL
Ultrasound images were digitized online and saved. Analyses of dia-
EDTA and ascorbic acid. The samples were analysed by HPLC. The
meter changes were conducted offline (Tom Tec Imaging Systems) by
HPLC detection system consisted of an Agilent 1100 (Agilent
two different investigators blinded to subject treatment.
Technology, San Diego) with a binary pump, thermostatted autosam-pler, column oven, photodiode array detector, and a data system withAgilent 1100 ChemStation software. The column was eluted at 358C
Endothelial nitric oxide synthase activity
with a binary gradient of 100% solution A (9% acetonitrile, 2%
acetic acid, containing 20 mg/mL EDTA) for 10 min, 68% solution Aand 32% of solution B (80% acetonitrile, 2% acetic acid, containing
Bovine aortic endothelial cells (BAEC) were maintained in EGM-MV
20 mg/mL EDTA) for 10 min at a flow rate of 1.0 mL/min. The
(endothelial cell growth medium), supplemented with 5% fetal
eluent was monitored at 278 nm. The signals were verified using UV
bovine serum, 10 pg/mL endothelial growth factor, 1 mg/mL hydro-
spectra (dioden array detector) and comparisons of the retention
cortisone, 12 mg/mL bovine brain extract, and 0.1% gentamicin. For
times with reference compounds. Quantification was carried out
experiments, cells in 6 cm dishes were incubated for 30 min in
using the relative response factor (RRF) concept of ISO 14505:2.
1.5 mL HEPES [4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid]buffer, pH 7.4, containing, in mmol/L, NaCl 145, KCl 5, MgSO4 1,
HEPES-Na 10, glucose 10, and CaCl2 1, followed by treatment with100 mL of black tea for 15 min. Tea and tea with milk were prepared
A two-step testing procedure was performed for the comparison of
as described earlier. Individual milk proteins were added to tea at
the three beverages: water, black tea, and tea with milk. In cases of
900 mg/mL. Endothelial nitric oxide synthase (eNOS) activity was
overall significance, pairwise tests were performed for the three
assessed by formation of L-[3H]citrulline from L-[3H]arginine after
possible comparisons between beverages. For three conditions and
separation of the amino acids by cation-exchange chromatography,
overall significance, no further adjustment for multiple testing
as described.11 Briefly, stimulation was initiated by addition of tea
was necessary. Since time points and beverages were not balanced,
beverages, 10 mmol/L cold L-arginine, and 3 mCi/mL L-[3H]arginine.
all comparisons between beverages were adjusted for a time effect
After 15 min, the reaction was terminated with ice-cold stop solution
by use of a linear model. The dependent structure of the data was
containing 5 mmol/L L-arginine and 4 mmol/L EDTA. Cells were
taken into account by use of generalized estimating equations. No
denatured with 96% ethanol, and after evaporation, the soluble
time effects or time vs. treatment interactions were found. All
cellular components were extracted with 20 mmol/L HEPES-Na, pH
statistical tests were two-sided (level of significance 0.05). The
5.5. L-[3H]citrulline was separated from L-[3H]arginine by Dowex
statistical analysis was performed using SPSS, Release 12.0.1, and
chromatography, and L-[3H]citrulline formation was quantified by
SAS, Release 9.1. All values are expressed as mean + SD in the
table and mean + SEM in the figures.
Measuring of eNOS activity in endothelial cells
FMD is evoked by nitric oxide generated by eNOS during ashort period of shear stress.13,14 We therefore measured
Baseline characteristics of the study group are summarized
generation of nitric oxide in response to tea with or
in Table 1. Endothelial function was assessed by measuring
without milk in cell culture experiments. Tea increased
FMD of the forearm brachial artery in 16 healthy females,
eNOS activity to more than 400% in BAEC. Addition of 10%
before and 2 h after ingestion of 500 mL water (control),
milk to tea completely eliminated the rise in eNOS activity
black tea alone, or black tea with 10% milk in a crossover
(Figure 2, upper panel). To identify the milk compounds
study. Whereas tea significantly increased FMD compared
responsible for the inhibiting effects, we performed exper-
with control, this effect was completely prevented by inges-
iments with single milk proteins. The major proteins in
tion of tea with milk (Figure 1A). In contrast, endothelial-
milk are a-casein (13 mg/mL), b-casein (9.3 mg/mL),
independent vasodilation (NMD) was not affected by
k-casein (3.3 mg/mL), a-lactalbumin (1.2 mg/mL), b-lacto-
addition of milk to tea (Figure 1B).
globulin (3.2 mg/mL), and serum albumin (0.4 mg/mL).15Individual milk proteins were added to tea at 900 mg/mLto avoid the influence of different amounts of protein perse. This amount corresponds to 9 mg/mL of protein concen-
Baseline characteristics of the study population
tration in the milk, after 10% of milk is added to tea. Allthree caseins blunted eNOS activity to an extent similar to
milk, whereas equal amounts of bovine serum albumin
(BSA), a-lactalbumin, and b-lactoglobulin had little effects
(Figure 2, upper panel). The activity of eNOS is regulated
by phosphorylation of the enzyme.16 Correspondingly, milk
and single milk caseins blocked tea-induced eNOS phos-
phorylation at Ser1179, whereas the other three milk proteins
were without effect (Figure 2, lower panel).
To extend these findings to a functional model, we deter-mined vasodilation in isolated rat aortic rings. Addition oftea cumulatively relaxed precontracted rat aortic rings,which
Similarly, addition of 10% milk completely inhibitedtea-induced relaxation (Figure 3A). In corroboration of ourdata in endothelial cells, addition of b-casein to tea
Changes in FMD and NMD after consumption of tea with and
without milk in humans. (A) A total of 16 volunteers consumed water, blacktea, or black tea with 10% milk, and changes in FMD were measured. FMDsignificantly (P , 0.01 compared with water) increased after consumption
Effect of milk and individual milk proteins on tea-induced nitric
of black tea. Addition of milk to tea suppressed the vasodilatory effects of
oxide production in endothelial cells. Cells were treated for 15 min with
tea (P , 0.01 compared with tea alone). (B) Beverages were consumed as
the indicated beverages, and eNOS activity was measured (upper panel).
in (A), and NMD was measured after sublingual application of nitroglycerin
Western blot showing the phosphorylation of eNOS (lower panel) was per-
spray (0.4 mg). FMD and NMD were defined as the maximum percentage
formed with an antibody specific to the eNOS Ser1179 phosphorylation site.
change in diameter compared with baseline measurement.
The western blot is representative from three independent experiments.
inhibited relaxation of aortic rings, whereas BSA had little
markedly decreased the concentrations of various catechins
in tea, whereas the contents, for example, of caffeine,gallic acid, and others were not affected (Table 2).
Tea polyphenols have been shown to interact with pro-teins.17 In an attempt to elucidate the underlying mechan-
ism for the diminished biological activities of tea after
The most striking finding of our study is that addition of milk
addition of milk, we measured the concentrations of
to black tea completely prevents the biological activity of tea
various tea compounds, including the catechins, in our tea
in terms of improvement of endothelial function. Our results
preparations. The concentrations of single tea compounds
thus provide a possible explanation for the lack of beneficial
were determined before, and in the supernatants, after cen-
effects of tea on the risk of heart disease in the UK, where
trifugation of the tea beverages at 13 000 g for 20 min.
milk is usually added to tea.18 To follow the common practice
Contents of individual tea compounds without addition of
of drinking tea in the UK, we added 10% milk to our black tea
milk did not significantly change upon centrifugation.
preparations. The well-established health benefits of tea,
However, addition of 10% milk to tea selectively and
as described by numerous studies,1–3 are mainly attributedto various flavonoids, especially catechins.19 Previously,we
epigallocatechin-3-gallate (EGCG), induces eNOS activationin endothelial cells and leads to vasorelaxation in rat aorticrings.11 In the present study, we found a particular, selectivedecrease in the concentrations of a number of catechins aftercentrifugation of freshly brewed tea with milk compared withtea without milk, which suggests complex formation between
catechins and milk proteins. Concentrations of other teacompounds were not affected by addition of milk. It was pre-viously reported that polyphenols can bind to proteins,20,21and interaction between flavanoids and proteins affects
their antioxidant capacity in vitro.22 There is some evidencethat
proline-rich proteins such as caseins.23 A very recent studydemonstrated the non-covalent cross-linking of EGCG bycaseins, emphasizing the interaction of tea catechins with
Interactions of food-derived flavonoids with milk proteins
may impede their physiological effects. An in vitro gastro-intestinal model to simulate the conditions in the humandigestive tract demonstrated that addition of milk to teainhibited its antimutagenic activity.25 Tea possesses strongantioxidant properties, in vitro and in vivo, that areaffected by addition of milk.26,27 In analogy, consumptionof dark chocolate that contains epicatechin, but not milkchocolate or dark chocolate with extra milk, increased theantioxidant capacity of human blood plasma.28 However, itshould be noted that other studies failed to establish aneffect of milk on antioxidant properties of tea.29,30 The
Tea-induced nitric oxide-dependent vasorelaxation in rat aortic
reasons for these discrepant findings are largely unknown
rings after addition of milk and individual milk proteins to tea. (A)Precontracted rat aortic rings were treated with water (control), tea alone,
but may be attributed to different physiological/experimen-
or tea with 10% milk, and vasorelaxation was determined. L-NAME indicates
tal endpoints (e.g. in vitro and in vivo, and assays for
NOS-inhibitor. Vasorelaxation is expressed as percent of contraction. (B)
measurements of antioxidant activities).
Rat aortic rings were treated with water (control), tea alone, tea with
In conclusion, milk may counteract the favourable health
b-casein, or tea with BSA, and vasorelaxation was determined as in (A).
effects of tea on vascular function. The finding that the
Data are mean + SEM from the indicated numbers of experiments.
Concentrations of tea ingredients (mmol/L)
TB, theobromine; TG, theogallin; EC, epicatechin; EGC, epigallocatechin; ECG, epicatechin gallate; EGCG, epigallocatechin gallate.
aTea was centrifuged at 13 000 g for 20 min.
tea-induced improvement of vascular function in humans is
activates endothelial nitric oxide synthase by a phosphatidylinositol-
completely attenuated after addition of milk may have
3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependentpathway and leads to endothelial-dependent vasorelaxation. J Biol
broad implications on the mode of tea preparation and con-
sumption. In addition, it indicates that caution is warranted
12. International Organization for Standardization. Determination of sub-
in the design of studies involving nutritional flavonoids.
stances characteristic of green and black tea. Part 2. Content ofcatechins in green tea. Method using high-performance liquid chromato-graphy. ISO 14502-2-2005.
13. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C,
Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of
There was no funding or support for this study. We are grateful to
human peripheral conduit arteries in vivo. Circulation 1995;91:
¨ft, Angelika Vietzke and Wanda Michaelis for
their excellent technical assistance.
14. Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA.
Conflict of interest: none declared.
endothelium-derived nitric oxide. Am J Physiol 1996;270:H1435–H1440.
15. Etzel MR. Manufacture and use of dairy protein fractions. J Nutr
16. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM.
Activation of nitric oxide synthase in endothelial cells by Akt-dependent
1. Stensvold I, Tverdal A, Solvoll K, Foss OP. Tea consumption relationship to
phosphorylation. Nature 1999;399:601–605.
cholesterol, blood pressure, and coronary and total mortality. Prev Med
17. Brown PJ, Wright WB. An investigation of the interactions between milk
proteins and tea polyphenols. J Chromatogr 1963;11:504–514.
2. Sano J, Inami S, Seimiya K, Ohba T, Sakai S, Takano T, Mizuno K. Effects of
18. Hertog MG, Sweetnam PM, Fehily AM, Elwood PC, Kromhout D.
green tea intake on the development of coronary artery disease. Circ J
Antioxidant flavonols and ischaemic heart disease in a Welsh population
of men: the Caerphilly Study. Am J Clin Nutr 1997;65:1489–1494.
3. Nakachi K, Matsuyama S, Miyake S, Suganuma M, Imai K. Preventive
19. Graham HN. Green tea composition, consumption, and polyphenol
effects of drinking green tea on cancer and cardiovascular disease: epide-
chemistry. Prev Med 1992;21:334–350.
miological evidence for multiple targeting prevention. Biofactors
20. Papadopoulou A, Frazier RA. Characterization of protein–polyphenol
interactions. Trends Food Sci Technol 2004;15:186–190.
4. Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian
21. Siebert KJ, Troukhanova NV, Lynn PY. Nature of polyphenol–protein inter-
JO, Vita JA. Predictive value of noninvasively determined endothelial
actions. J Agric Food Chem 1996;44:80–85.
dysfunction for long-term cardiovascular events in patients with periph-
22. Arts MJ, Haenen GR, Voss HP, Bast A. Masking of antioxidant capacity by
eral vascular disease. J Am Coll Cardiol 2003;41:1769–1775.
the interaction of flavonoids with protein. Food Chem Toxicol 2001;
5. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases:
the role of oxidant stress. Circ Res 2000;87:840–844.
23. Luck G, Liao H, Murray NJ, Grimmer HR, Warminski EE, Williamson MP,
6. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary
Lilley TH, Haslam E. Polyphenols, astringency and proline-rich proteins.
vasodilator dysfunction on adverse long-term outcome of coronary
heart disease. Circulation 2000;101:1899–1906.
7. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar
24. Jobstl E, Howse JR, Fairclough JP, Williamson MP. Noncovalent cross-
D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the
linking of casein by epigallocatechin gallate characterized by single
extent and severity of coronary artery disease. Atherosclerosis
molecule force microscopy. J Agric Food Chem 2006;54:4077–4081.
25. Krul C, Luiten-Schuite A, Tenfelde A, van Ommen B, Verhagen H,
8. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F,
Havenaar R. Antimutagenic activity of green tea and black tea extracts
Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D,
studied in a dynamic in vitro gastrointestinal model. Mutat Res
Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of
endothelial-dependent flow-mediated vasodilation of the brachial
26. Serafini M, Ghiselli A, Ferro-Luzzi A. In vivo antioxidant effect of green
artery: a report of the International Brachial Artery Reactivity Task
and black tea in man. Eur J Clin Nutr 1996;50:28–32.
Force. J Am Coll Cardiol 2002;39:257–265.
27. Langley-Evans SC. Consumption of black tea elicits an increase in plasma
9. Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-
antioxidant potential in humans. Int J Food Sci Nutr 2000;51:309–315.
mediated dilatation: implications for the assessment of endothelial func-
28. Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A.
Plasma antioxidants from chocolate. Nature 2003;424:1013.
10. Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P,
29. Leenen R, Roodenburg AJ, Tijburg LB, Wiseman SA. A single dose of tea
Deanfield JE, MacAllister RJ. Heterogenous nature of flow-mediated
with or without milk increases plasma antioxidant activity in humans.
dilatation in human conduit arteries in vivo: relevance to endothelial
dysfunction in hypercholesterolemia. Circ Res 2001;88:145–151.
30. Reddy VC, Vidya Sagar GV, Sreeramulu D, Venu L, Raghunath M. Addition
11. Lorenz M, Wessler S, Follmann E, Michaelis M, Du
of milk does not alter the antioxidant activity of black tea. Ann Nutr
Stangl K, Stangl V. A constituent of green tea, epigallocatechin-3-gallate,
AUDI AG Product and Technology Communications 85045 Ingolstadt, Germany Tel: +49 (0)841 89-32100 Fax: +49 (0)841 89-32817 March 2012 The Audi A8 hybrid – systematic efficiency The equipment and data specified in this document refer to the model range offered in Germany. Subject to change without notice; errors and omissions excepted. Efficiency on a grand scale – the Audi A
DNAA-Konsensus zu antiretroviraler Therapie aus neurologischer Sicht Deutsche Neuro-AIDS-Arbeitsgemeinschaft (DNAA) I. Klinische Vorbemerkungen Das humane Immundefizienzvirus (HIV) kann das periphere und das zentrale NervensystemDer HIV-1-assoziierte Demenz-Komplex (HADK) als häufigste, zentralnervöse Manifestationeiner HIV-Infektion ist gekennzeichnet durch kognitive, motorische und