Flavonoid supplement improves leg health and reduces fluid retention in pre-menopausal women in a double-blind, placebo-controlled study.Summary
Flavonoid extracts derived from plant foods have been shown to benefit certain types of fluid retention. However, no studies have investigated these compounds for use in premenstrual premenstrual /pre·men·stru·al/ (pre-men´stroo-al) occurring before menstruation.
Of or occurring in the period just before menstruation. fluid retention, a complaint common among women with otherwise normal menstrual cycles. Therefore, we conducted a double-blind, placebo-controlled, pilot study into the effect of a daily flavonoid extract (Colladeen[R], 320 mg oligomeric procyanidins) on premenstrual fluid retention. Fluid retention was assessed at baseline and throughout 4 menstrual cycles of the intervention using validated questionnaires. Leg girth GIRTH., A girth or yard is a measure of length. The word is of Saxon origin, taken from the circumference of the human body. Girth is contracted from girdeth, and signifies as much as girdle. See Ell. was also measured at baseline and at the end of the study.
Thirty subjects completed the study (n = 18 active treatment; n = 12 placebo). Although no significant changes in leg girth measurements were noted, there was a significant improvement in subjective "leg health" scores after flavonoid treatment compared to placebo (p = 0.013). Furthermore, this was accompanied by an improvement in reported premenstrual fluid retention nearing significance (p = 0.066). We conclude that flavonoids flavonoids,
n.pl common plant pigment compounds that act as antioxidants, enhance the effects of vitamin C, and strengthen connective tissue around capillaries. supplements may provide a new therapeutic direction to counter premenstrual fluid retention and improve leg health. A larger study is now warranted.
Key words: flavonoids, fluid retention, leg health, premenstrual, grapeseed extract, dietary supplement
Fluid retention, a common condition in women, is normally unaccompanied by evidence of cardiac, renal or hepatic disease. Various terms have been used to describe this benign form of fluid retention: idiopathic oedema oedema
see edema. , orthostatic orthostatic /or·tho·stat·ic/ (or?tho-stat´ik) pertaining to or caused by standing erect.
Relating to or caused by standing upright, as hypertension. oedema, cyclical oedema and fluid retention syndrome. Fluid retention of this type may present as a premenstrually-exacerbated occurrence (Abraham, 1981), or a non-cyclical event (Hechter et al. 1942). Sufferers frequently describe their legs as "heavy", "swollen" and "tight" on exertion (Anon, 1998). In addition, the abdomen, hands, breasts and area around the eye are frequently affected.
Several hypotheses have been postulated to explain the underlying aetiology aetiology
see etiology. of fluid retention (Christie et al. 2001). Research findings support the hypothesis that magnesium dysregulation may be involved in some subjects. Magnesium supplementation has been found to reduce symptoms of premenstrual fluid retention (Walker et al. 1998) as well as non-cyclical fluid retention (Barbeau et al. 1973). In the UK, the orthodox approach for the symptomatic relief of fluid retention is through the use of diuretics. Unfortunately, diuretic diuretic (dī'yərĕt`ĭk), drug used to increase urine formation and output. Diuretics are prescribed for the treatment of edema (the accumulation of excess fluids in the tissues of the body), which is often the result of underlying treatment with drugs is not without side effects Side effects
Effects of a proposed project on other parts of the firm. (renal failure, gastrointestinal upset, cramps and decreased blood pressure have been reported: MIMS MIMS Music Is My Savior (music album)
MIMS Medical Information Management System
MIMS Multimedia Integrated Modeling System (US EPA)
MIMS Membrane Introduction Mass Spectrometry , 2002) and is frequently associated with poor clinical outcomes (MIMS, 2002).
Physicians in mainland Europe often prescribe flavonoid extracts for the relief of symptoms of fluid retention, following the dissemination of findings from German and Italian studies (Christie et al. 2001). Flavonoid extracts used in these studies are derived from grape seed (Vitis vinifera), bilberry bilberry
Low-growing deciduous shrub (Vaccinium myrtillus) of the heath family, found in woods and on heaths, chiefly in hilly districts of Britain, northern Europe, and Asia. The stiff stems bear small egg-shaped leaves and small rosy flowers tinged with green. fruit (Vaccinium myrtillus) and cranberry fruit (Vaccinium macrocarpon), and are standardised on their contents of oligomeric procyanidins (OPCs).
It has been suggested that flavonoids reduce symptoms of fluid retention through some or all of a number of mechanisms: (I) the protection and support of collagen-rich structures (Monboisse et al. 1984), (II) the reduction of metabolites known to increase vascular permeability (Kuhl et al. 1984), (III) the enhancement of intracellular vitamin C (Benstath et al. 1936; Gabe and Parrot, 1951; Rusenyak et al. 1961) and (IV) the protection of tissues from oxidative damage (Dewick, 1997).
Preclinical studies have shown flavonoid extracts to reduce experimentally-induced fluid retention and associated capillary permeability (Bonacina et al. 1973; Lietti et al. 1976; Lietti and Forni, 1976; Jonadet et al. 1983). Furthermore, clinical studies have shown a benefit of flavonoid extracts for certain microcirculatory disorders associated with oedema (reviewed in Christie et al. 2001), including tissue recovery following surgery. However, studies investigating the efficacy of these extracts to alleviate symptoms of premenstrual fluid retention are lacking. Therefore, the aim of this study was to investigate the effects of a commercially-available flavonoid extract on premenstrual fluid retention.
Materials and Methods
Normally menstruating women suffering from fluid retention, were recruited from articles in womens' magazines and national newspapers in the UK, following a press release. Women already using medication for fluid retention, (including flavonoid extracts), were excluded from the study. Further exclusion criteria were heart, kidney or liver disease, and malignancy. Written informed consent was obtained from each volunteer, and each volunteers' GP was notified of their patients' participation in the study. The study was started in the autumn and proceeded through the winter. It was allowed by the Ethics and Research Committee of The University of Reading and the West Berkshire Local Research and Ethics Committee.
The duration of the study was five menstrual cycles. The first cycle was used to collect baseline data, and treatment was given over the remaining four cycles. Prior to the study, subjects were randomised Adj. 1. randomised - set up or distributed in a deliberately random way
irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" to receive a daily supplement of either a flavonoid extract containing 320 mg of OPCs (Colladeen[R], manufactured by Lamberts Healthcare Limited, Century Place, Lamberts Road, Tunbridge Wells, Kent, TN2 3EQ, UK) or a physically-matched placebo. A randomisation list for two treatments was created using random number tables according to the method described by Pocock (1983). Block randomisation was used to obtain balanced groups with women of BMI BMI body mass index.
body mass index
Body mass index (BMI)
A measurement that has replaced weight as the preferred determinant of obesity. (Body Mass Index) > or <30. Numbered pill boxes containing the supplements were assigned consecutively to participants. Colladeen[R] capsules provided 80 mg of oligomeric procyanidins derived from a mixture of Grape seed (Vitis vinifera; 66.4 mg OPCs; 85% OPC (1) (OpenGL Performance Characterization) A project group within GPC that manages OpenGL benchmarks. OPC endorses the Viewperf and GLperf benchmarks. Viewperf was created by IBM and OPC provides viewsets for it, which are combinations of tests using specific extract). Cranberry fruit (Vaccinium macrocarpon; 12.6 mg OPCs; 16.4% OPC extract) and Bilberry fruit (Vaccinium myrtillus; 0.93 mg OPCs; 25% OPC extract). OPCs were determined according to the method of Gabetta et al. (2000). Dimeric OPCs were determined by HPLC HPLC high-performance liquid chromatography.
high performance liquid chromatography.
HPLC High-performance liquid chromatography Lab instrumentation A highly sensitive analytic method in which analytes are placed thermospray mass spectrometry. Higher weight OPCs were determined by fractionation fractionation /frac·tion·a·tion/ (frak?shun-a´shun)
1. in radiology, division of the total dose of radiation into small doses administered at intervals.
2. over Sephadex[R] LH-20 resin and analysis of the isolated fractions by gel permeation chromatography Gel permeation chromatography (GPC) is a separation technique based on hydrodynamic volume (size in solution). Molecules are separated from one another based on differences in molecular size. This technique is often used for polymer molecular weight determination. and electrospray mass spectroscopy. The placebo capsules contained equal parts (w/w) of micro-crystalline cellulose and calcium phosphate. Subjects were instructed to take 4 capsules per day before meals (either Colladeen[R] or placebo), 2 capsules in the morning and 2 in the evening. To maintain the double-blind nature of the study, treatment allocation was known only to the project director (AFW AFW Air Force Weather
AFW Auxiliary Feedwater (Nuclear Power)
AFW Alliance Airport, Fort Worth (Airport Code)
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AFW Application Frame Work ) who had no direct contact with the volunteers.
BMI and typical dietary nutrient intakes were assessed at baseline and the end of the study in order to record any changes or differences between groups which might influence outcome. Dietary intake was estimated using a validated 3-day diet diary, and analysed using CompEat (Lifeline, Nutritional Services, Pond House, 21 Craven Hill, London, W2 3EN). Apart from energy and alcohol intake, particular attention was paid to the intakes of nutrients that may play a role in the pathogenesis of fluid retention: sodium, calcium, magnesium, potassium, vitamin B6 and vitamin C.
All physical measurements were made during clinical visits at baseline, and during the last cycle of the study. These appointments were scheduled for the premenstrual phase of each cycle. Tolerance to supplementation was assessed in a post-study questionnaire.
Subjects prospectively recorded their symptoms throughout the study in a menstrual diary (MD). The MD was made up of items from two questionnaires; (1) a 19-item "premenstrual symptoms" questionnaire modified from Moos (1968) and used previously by our group (De Souza et al. 2000), and (2) a 7-item "leg health" questionnaire (Lagrue et al. 1993). Each symptom in the diary was scored on a 5-point scale (0 -- very mild; 1 -- mild; 2 -- moderate; 3 -- severe and 4 -- very severe). Scored symptoms were categorised into subgroups as shown in Table 1. For each individual, "premenstrual" scores of each symptom subgroup were calculated. These "premenstrual" scores were calculated as the mean of daily subgroup scores over the 7 days prior to menstruation. "Postmenstrual post·men·stru·al
Of or occurring in the time following menstruation. " scores were calculated similarly using scores from the 7 days following menstruation (days 8-14 of the cycle).
Leg girth was monitored as an objective measure of fluid retention, using the Leg-O-Meter (Breard et al. 1998), a specially-designed instrument allowing an accurate, reproducible measure of leg girth. Blood pressure was monitored as a secondary outcome using an Omron 703CP automatic BP monitor (Omron Terminals Ltd, Chessington, UK). At each clinical visit, three readings of systolic Systolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest. and diastolic blood pressure Diastolic blood pressure
Blood pressure when the heart is resting between beats.
Mentioned in: Hypertension (BP) were taken at rest. For each set of three blood pressure readings the first value was discarded and the mean of the last two used for the analyses.
In the absence of relevant data from similar studies on which to base a power calculation, the number of volunteers was limited by practical considerations. A two-sample t-test was used to confirm lack of baseline differences in outcome data between the two treatment groups. Final cycle premenstrual subgroup scores were compared between the two treatment groups using Analysis of Covariance Covariance
A measure of the degree to which returns on two risky assets move in tandem. A positive covariance means that asset returns move together. A negative covariance means returns vary inversely. (ANCOVA ANCOVA Analysis of Covariance ), using comparable baseline scores as covariate. Mean differences were deemed statistically significant if p < 0.05. Symptom subgroups "leg health" and "PS-Hydration" comprised the primary outcomes of the study. Similar analyses were used for other outcome data. Statistical analyses were performed using MINITAB (Minitab Inc., 3081 Enterprise Drive, State College, PA 16801-3008, USA).
Study population characteristics
Thirty-six women were recruited onto the study, and 30 completed the protocol (n = 18 Colladeen[R]; n = 12 placebo). Reasons for dropout (1) On magnetic media, a bit that has lost its strength due to a surface defect or recording malfunction. If the bit is in an audio or video file, it might be detected by the error correction circuitry and either corrected or not, but if not, it is often not noticed by the human were personal in all cases, and so none were attributed to treatment. Table 2 compares the personal characteristics of subjects completing the study. Approximately 50% of subjects reported that their fluid retention was a premenstrually exacerbated condition, and the vast majority had been suffering from the problem for longer than 2 years. The oral contraceptive was currently used by 17% of subjects in the flavonoid group and 33% in the placebo group.
Mean ([+ or -]s.e.m.) baseline BMI was 27.5 ([+ or -]1.2) in the flavonoid treatment group, and 26.7 ([+ or -]1.6) in the placebo group. BMI increased significantly in both treatment groups over the course of the study (+2.2% for Colladeen[R]; +1.5% for placebo), although these changes were not significantly different between the treatments. Interestingly, mean daily total energy intake ([+ or -]s.e.m.) in both flavonoid and placebo groups were lower at baseline (1768 [+ or -] 126 versus 1688 [+ or -] 103 kcal, respectively) than in the last cycle of the study (1899 [+ or -] 83 versus 1914 [+ or -] 101 kcal, respectively). The treatment groups showed no significant differences in their intake of nutrients at baseline (data not shown), except that the flavonoid treatment group had a significantly lower mean daily sodium intake compared to the placebo group (2088 [+ or -] 133 versus 2551 [+ or -] 93 mg, respectively) and a significantly higher daily mean alcohol intake (8.5 [+ or -] 2.4 versus 2.9 [+ or -] 1.1 g, respectively). However, these differences are unlikely to have impacted on outcome, as no differences between intakes were found between the two groups at the end of the study. Mean potassium intakes were lower than the Reference Nutrient Intake (RNI (Raw Native Interface) A programming interface in Microsoft's Java Virtual Machine used for calling native Windows elements such as GUI routines. RNI is Microsoft's Windows-oriented counterpart of Sun's JNI (Java Native Interface). ) of 3500 mg per day (DH, 1991) in both supplement groups at baseline (2835 [+ or -] 211 versus 2596 [+ or -] 157 mg, respectively) and at the end of the study (3039 [+ or -] 188 versus 3183 [+ or -] 181, respectively).
Mean premenstrual symptom scores over the 5 cycles of the study are shown in Table 3. There were no significant differences between the treatment groups at baseline. However, after 4 cycles of treatment the "leg health" scores of subjects receiving the flavonoid supplement were significantly lower than those receiving placebo (p = 0.013). Also at this time, subjects who had received the flavonoids had lower "PS-Hydration" scores, and this difference only just missed statistical significance (p = 0.066). There were no other significant differences between the treatments in any of the other premenstrual subgroup scores.
Fig. 1a and b show premenstrual and postmenstrual "leg health" scores for the two treatment groups. From cycle 2 onwards the daily flavonoid supplementation appeared to specifically and accumulatively reduce premenstrual fluid retention, without a sustained effect on postmenstrual fluid retention. By contrast, reduction in premenstrual leg scores induced by placebo treatment were not sustained by the end of the study.
Leg girth measurements were not significantly different between the treatment groups at baseline (e.g. mean [[+ or -]s.e.m.] left thigh girth at baseline: 60.0 [[+ or -]1.39] flavonoid group and 60.9 [[+ or -]2.08] placebo group), nor after treatment. Similarly, no significantly different values in diastolic Diastolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are being filled with blood. During this phase, the ventricles are at their most relaxed, and the pressure against the walls of the arteries is at its lowest. or systolic blood pressure Systolic blood pressure
Blood pressure when the heart contracts (beats).
Mentioned in: Hypertension readings were seen between the treatment groups at baseline (e.g. mean [[+ or -]s.e.m.] systolic blood pressure at baseline: 122.4 [[+ or -]3.13] flavonoid group and 123.4 [[+ or -]3.14] placebo group), nor after treatment.
The post-study questionnaire revealed a high degree of tolerance to the test materials administered. One of the volunteers from the flavonoid treatment group reported a change in bowel habit, one subject mild headache and a further individual reported increased urinary output. Two volunteers from the placebo group noticed mild gastrointestinal changes during the study. No serious side effects were recorded for either treatment.
[FIGURE 1 OMITTED]
We conducted a randomised, placebo-controlled study to investigate the efficacy of a daily flavonoid supplement based on grapeseed extract for 4 months in the treatment of fluid retention. The results showed the flavonoid supplement to be superior to placebo for enhancing leg health and to hold promise for the alleviation of subjective symptoms of premenstrual fluid retention. To our knowledge this was the first such study examining the effects of a flavonoid extract for symptoms associated with premenstrual fluid retention.
Overall, subjects in the study exhibited a premenstrual exacerbation of symptoms of fluid retention (Fig. 1a and b), indicating that fluid retention was, at least in most of the women in the study, a cyclical phenomenon. Flavonoids were more effective in reducing premenstrually exacerbated fluid retention (Fig. 1a), than fluid retention at other times of the cycle. It has been suggested that all women are to some extent fluid retaining (Thorn, 1968), as there is a greater tendency for womens'compared with mens'ankles to swell in hot weather and on prolonged standing. Premenstrual fluid retention may represent an exaggeration of normal fluid-retaining mechanisms. The interesting observation from this study, that flavonoids specifically reduced premenstrual fluid retention, suggests that these compounds may help to normalise premenstrual fluid balance through their influence on these mechanisms, rather than acting as a diuretic via renal stimulation.
Subjects in this study had low intakes of potassium compared with the RNI (DH 1991). As fruit and vegetables are the main source of potassium in the diet, this finding suggests that the women had low intakes of fruit and vegetables and were, hence, unlikely to have met the recommended intake of 5 portions of fruit and vegetables per day. If this were so, they would also have had low intakes of flavonoids, which are mostly confined to this food group. Therefore, it might be that flavonoid supplementation is useful for normalising premenstrually exacerbated fluid retention in women whose intakes of fruit and vegetables are low.
The objective measures of leg girth showed no differences between flavonoid and placebo supplementation at the end of the study. Hence, these observations did not confirm the findings of a benefit in symptoms discussed above. The reason for this may be due to a lack of correlation between subjective complaints of fluid retention and objective signs of fluid retention, a phenomenon which has been observed previously (Denning et al. 1990). Furthermore there may have been flaws in the study protocol regarding the timing of leg girth measurement, which we were unaware of when the study was planned. A specific sign of fluid retention in women is a diurnal diurnal /di·ur·nal/ (di-er´nal) pertaining to or occurring during the daytime, or period of light.
1. Having a 24-hour period or cycle; daily.
2. weight variation (Thorn, 1968), due to fluid accumulation during the day, as subjects adopt an upright posture. At night, when subjects adopt a recumbent recumbent /re·cum·bent/ (re-kum´bent) lying down.
Lying down, especially in a position of comfort; reclining. position, enhanced diuresis diuresis /di·ure·sis/ (di?u-re´sis) increased excretion of urine.
osmotic diuresis that resulting from the presence of nonabsorbable or poorly absorbable, osmotically active substances in the ensues, with a return to normal weight by morning. In this present study, all leg measurements were taken in the morning rather than twice per day, so changes that may have occurred later in the day would not have been detected.
Although BMI increased in both treatment groups after 4 cycles of treatment, together with an increased energy intake, it is unlikely that this would have had substantial impact on outcome since both groups experienced the same effect. Our study commenced in the autumn and proceeded through the winter--a time when intake of food and body weight have been reported to increase (Shahar et al. 2001). The impact on outcome of the higher contraceptive use among the placebo group (33% versus 17% flavonoid group) is not possible to predict due to a lack of clear association between leg health and contraceptive use in the literature. However, fluid retention is a reported side-effect of the oral contraceptive pill (MIMS, 2002). Therefore it cannot be ruled out that the higher proportion of contraceptive pill users in the placebo group introduced some element of bias in our results. This is because the placebo group may have showed a diminished response to placebo due to the compounding effects of the oral contraceptive on fluid retention.
In conclusion, the findings of this randomised, double-blind pilot study, showed a beneficial effect on leg health and symptoms of premenstrual fluid retention of a daily supplementation of 320 mg of OPC flavonoids for 4 months compared with placebo. A larger-scale RCT RCT Randomized Controlled Trial
RCT Regimental Combat Team (infantry regiment with their own artillery, engineers, medical and tanks)
RCT Rollercoaster Tycoon
RCT Randomized Clinical Trial
RCT Rhondda Cynon Taff is now warranted to confirm these findings.
Table 1. Symptom subgroups scored in the menstrual diary. Symptom Maximum Symptoms (number of subgroup daily score symptoms per category) PS-Anxiety 16 Nervous tension, mood swings, irritability, anxiety (4) PS-Craving 24 Headaches, craving for sweets, increased appetite, heart pounding, fatigue, dizziness or faintness (6) PS-Depression 20 Depression, forgetfulness, confusion, insomnia, violent feeling (5) PS-Hydration 16 Weight gain, swelling of extremities, breast tenderness, abdominal bloating (4) Leg health 28 Swelling, heaviness, lack of agility, pain, varicosity, cramps, itchiness (7) Table 2. Mean ([+ or -]s.e.m.) baseline characteristics of subject groups completing the study (n = 18 flavonoid; n = 12 placebo). Characteristic Treatment group Flavonoid Placebo Age (yrs) 40.7 (1.4) 36.5 (2.1) Height (m) 1.60 (0.02) 1.70 (0.03) Weight (kg) 71.6 (3.6) 71.6 (4.5) Body Mass Index (BMI) (kg/[m.sup.2]) 27.5 (1.2) 26.7 (1.6) Regular menstrual bleeding (%) 100 100 Reported premenstrual 50 42 exacerbation of fluid retention (%) Duration of fluid retention: (i) 1-2 years, (%) (i) 0 (i) 8 (iii) More than 2 years, (%) (iii) 100 (iii) 92 Current oral contraceptive 17 33 pill-users, (%) Table 3. Mean premenstrual scores ([+ or -]s.e.m.) before and at the end of 4 months of daily flavonoid or placebo supplementation. (Premenstrual scores are means of daily scores over 7 days). Months of Symptom Maximum Flavonoid treatment supplementation Sub-group daily score n = 18 Score % max. score 0 (baseline) PS--Anxiety 16 2.27 (0.57) 14.2 PS--Craving 24 2.53 (0.44) 10.5 PS--Hydration 16 2.97 (0.55) 18.6 PS--Depression 20 0.98 (0.27) 4.9 Leg score 28 5.09 (0.57) 18.2 1 PS--Anxiety 16 2.21 (0.58) 13.8 PS--Craving 24 2.10 (0.56) 8.8 PS--Hydration 16 2.69 (0.57) 16.8 PS--Depression 20 1.37 (0.60) 6.8 Leg score 28 4.94 (0.80) 17.6 2 PS--Anxiety 16 1.83 (0.49) 11.4 PS--Craving 24 2.03 (0.54) 8.4 PS--Hydration 16 2.18 (0.51) 13.6 PS--Depression 20 1.01 (0.37) 5.0 Leg score 28 3.66 (0.61) 13.7 3 PS--Anxiety 16 1.56 (0.45) 9.8 PS--Craving 24 1.83 (0.39) 7.6 PS--Hydration 16 1.91 (0.39) 11.9 PS--Depression 20 0.96 (0.25) 4.8 Leg score 28 2.69 (0.38) 9.6 4 PS--Anxiety 16 1.50 (0.37) 9.4 PS--Craving 24 1.50 (0.32) 6.2 PS--Hydration 16 1.69 (0.39)* 10.6 PS--Depression 20 0.65 (0.23) 3.2 Leg score 28 2.83 (0.47) 10.1 [omega] Months of Symptom Placebo treatment supplementation Sub-group n = 12 Score % max. score 0 (baseline) PS--Anxiety 1.32 (0.59) 8.2 PS--Craving 2.32 (0.63) 9.6 PS--Hydration 3.30 (0.85) 20.6 PS--Depression 1.09 (0.49) 5.4 Leg score 4.82 (0.81) 17.2 1 PS--Anxiety 1.31 (0.59) 8.2 PS--Craving 1.58 (0.79) 6.6 PS--Hydration 2.88 (0.98) 18.0 PS--Depression 1.05 (0.53) 5.2 Leg score 4.33 (0.87) 15.5 2 PS--Anxiety 1.41 (1.00) 8.8 PS--Craving 2.17 (0.96) 9.0 PS--Hydration 3.36 (1.25) 21.0 PS--Depression 1.14 (0.92) 5.7 Leg score 4.08 (1.09) 14.6 3 PS--Anxiety 1.52 (0.70) 9.5 PS--Craving 1.60 (0.70) 6.6 PS--Hydration 3.06 (0.79) 19.1 PS--Depression 0.76 (0.47) 3.8 Leg score 3.20 (0.91) 11.4 4 PS--Anxiety 1.54 (0.72) 9.6 PS--Craving 1.52 (0.78) 6.3 PS--Hydration 3.16 (0.96) 19.8 PS--Depression 0.99 (0.61) 5.0 Leg score 4.90 (1.31) 17.5 [PSI], significant difference between treatments; p = 0.013 *, difference between treatments; p = 0.066
Thanks are due to Lamberts Healthcare Ltd for the donation of the supplements and support of the post-graduate studies of SC. Thanks also to Helen Wolfenden and Elizabeth Head for technical assistance on clinic days, and to Julie Corke at Lamberts for administrative assistance.
Abraham GE (1981) Premenstrual Tension--Current Problems. Obstetrics and Gynaecology 3: 1-39
Anon (1998) Swollen ankles--Patient factsheet. General Practitioner. Haymarket Medical Ltd, UK, 1998
Barbeau A, Rojo-Ortega JM, Brecht NM (1973) Deficience en magnesium et dopamine dopamine (dōp`əmēn), one of the intermediate substances in the biosynthesis of epinephrine and norepinephrine. See catecholamine.
One of the catecholamines, widely distributed in the central nervous system. cerebrale, cited in Durlach J. First Int. Symposium on Magnesium Deficit in Human Pathology. Paris Vittel F: 149-152
Bentsath A, Rusznyak ST. Szent-Gyorgyi A (1936) Vitamin nature of flavones. Nature 138: 798
Berard A, Kurz X, Zuccarelli F, Ducros J, Abenhaim L (1998) Reliability study of the Leg-O-Meter, an improved tape measure device, in patients with chronic venous insufficiency chronic venous insufficiency Venous insufficiency Vascular disease A condition characterized by poor flow of venous blood, especially in the leg veins Clinical Leg swelling, pain, cramps, risk of DVT of the leg. Angiology angiology /an·gi·ol·o·gy/ (an?je-ol´ah-je) the study of the vessels of the body; also, the sum of knowledge relating to the blood and lymph vessels.
n. 49: 169-173
Bonacina F, Galliani G, Pacchiano F (1973) Activity of anthocyanosides in acute inflammatory processes. Farmaco-Edprat 28: 428-434
Bonacina F, Pacchiano F (1974) Complementary activity of anthocyanosides in a preparation with anti-oedema and capillary-protective activity. Boll Chim Farm 113: 540-550
Christie S, Walker AF, Lewith GT (2001) Flavonoids--a new direction for the treatment of fluid retention? Phytother Res 15: 467-475
De Souza MC, Walker AF, Robinson PA, Bolland B (2000) A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens' Health Gend Based Med 9: 131-139
Dewick PM (1997) Medicinal natural products--a biosynthetic bi·o·syn·the·sis
Formation of a chemical compound by a living organism. Also called biogenesis.
bi approach. John Wiley and Sons, Chichester, UK
DH, Department of Health (1991) Dietary Reference Values for food energy and nutrients for the United Kingdom. Report on Health and Social Subjects No. 41. HMSO HMSO (in Britain) Her (or His) Majesty's Stationery Office
HMSO n abbr (BRIT) (= His (or Her) Majesty's Stationery Office) → distribuidor oficial de las publicaciones del gobierno del Reino Unido , London
Gabe M, Parrot JL (1951) Apport An apport is the transference of an article from an unknown source, to you, or another place by unknown means. The item can be anything, from coins and jewellery from ancient times, to modern objects such as watches and keys. de Ihistophysiologie a letude de la vitamine [C.sub.(2)] Prat Med 59: 1740-1744
Gabetta B, Fuzzati N, Griffini A, Lolla E, Pace R, Ruffilli T, Peterlongo F (2000) Characterisation of proanthocyanidins from grape seeds. Fitoterapia 71: 162-175
Hechter OL, Krohn L, Harris J (1942) Effects of oestrogen oes·tro·gen
Variant of estrogen.
see estrogen. and other steroids on capillary permeability. Endocrinology 30: 598-608
Jonadet M, Meunier MT, Bastide Bastides are fortified new towns built in medieval Languedoc, Gascony and Aquitaine during the thirteenth and fourteenth centuries, although some authorities count Mont-de-Marsan and Montauban, which was founded in 1144, as the first bastides. P (1983) Anthocyanosides from Vitis vinifera, Vaccinium myrtillus and Pinus maritimus. I. In vitro elastase elastase /elas·tase/ (e-las´tas) see pancreatic elastase.
An enzyme found especially in pancreatic juice that catalyzes the hydrolysis of elastin. inhibiting activities. II In vivo angioprotective activities. Pharm Belg 38: 41-46
Kuhl P. Shiloh R, Jha H, Murawski K, Zilliken F. (1984) 6,7,4'-trihydroxy isoflavan: a potent and selective inhibitor of 5-lipoxygenase in human and procine peripheral blood leukocytes. Prostaglandins 28: 783-804
Lagrue G, Behar A (1989) Oedematous OE`dem´a`tous
a. 1. (Med.) Pertaining to, or of the nature of, edema; affected with edema. syndromes caused by capillary hyperpermeability. Diffuse angioedema. J Mal Vasc 14: 231-235
Lietti A, Cristoni A, Picci M (1976) Studies on Vaccinium myrtillus anthocyanosides. Arzneim-Forsch 26: 829-832
Lietti A, Forni H (1976) Studies on Vaccinium myrtillus anthocyanosides II. Aspects of anthocyanidins pharmacokinetics in the rat. Arzneim-Forsch 26: 832-835
MIMS (1998) Monthly Index of Medical Specialities MIMS (Monthly Index of Medical Specialities) is a pharmaceutical prescribing reference guide published in the UK by Haymarket Group. The guide contains information about all drugs in the UK formulary. . Haymarket Medical Limited, UK
Monboisse JC, Braquet P, Borel P (1984) Oxygen-free radicals as mediators of collagen breakage. Agents and Actions 15: 49-50
Moos RH (1968) The development of a menstrual distress questionnaire. Psychosom Med 30: 853-67
Pocock SJ (1983) Clinical trials: a practical approach. John Wiley and Sons, Chichester, UK
Rusznyak I, Stark E, Folfi Buki B (1961) Sullazione della rutina e dellacido ascorbico sulla resistenza dei capillari. Minerva Med 52: 2238
Shahar DR, Yerushalmi N, Lubin F, Froom P, Shahar A, Kristal-Boneh E (2001) Seasonal variations in dietary intake affect the consistency of dietary assessment. Eur J Epidemiol 17: 129-133
Thorn GW (1968) Approach to the patient with "idiopathic edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. " or "periodic swelling". JAMA 206: 333-338
Walker AF, De Souza MC, Vickers MF, Abeyasekera S, Collins ML, Trinca LA (1998) Magnesium supplementation alleviates premenstrual symptoms of fluid retention. Journal of Womens' Health 7: 1157-1165
S. Christie (1), A. F. Walker (1), S. M. Hicks (1), and S. Abeyasekera (2)
(1) Hugh Sinclair Unit of Human Nutrition, The School of Biosciences, The University of Reading, Reading, UK
(2) School of Applied Statistics, The University of Reading, Reading, UK
Ann F. Walker, Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights, PO Box 226, Reading, RG6 6AP, UK
Tel.: 0118-931-8723; Fax: 0118-931-0800; e-mail: firstname.lastname@example.org