Mineral rich algae with pine bark improved pain, physical function and analgesic use in mild-knee joint osteoarthritis, compared to Glucosamine: A randomized controlled pilot trial.

INTRODUCTION: Osteoarthritis (OA) is characterised by synovial joint pain, functional disability and affects ∼13 % of people worldwide, of which ∼16-27 % report Knee-OA (KOA). Glucosamine (Glu) is the most widely used nutraceutical treatment for OA despite a lack of scientific consensus, therefore alternative nutraceutical treatments are required. The aim of this study was to investigate the effect of Lithothamnion species, seawater-derived magnesium and pine bark (Aq+) on pain, symptoms and improve physical function in symptomatic (sKOA), compared to Glu. METHODS: 358 participants were screened. In a double-blinded crossover pilot-trial, sKOA participant (n = 30) were randomly assigned to either the Glu group (2000 mg day-1) or Aq+ (3056 mg day-1) for 12 weeks (clinicaltrials.gov:NCT03106584). The Knee Injury and Osteoarthritis Outcome Score was used to assess subjective pain and symptoms. Timed-up-and-Go (TuG) and Six minute walking distance were used to assess functional change and analgesic use was recorded. RESULTS: Aq+ improved pain, with a large effect (P < 0.01, d' = 0.73, 95 %CI 0.201-1.265) and no change for Glu (d' = 0.38, P = 0.06). Only Aq+ improved pain (P < 0.05) for males (d' = 0.91, 95 %CI 0.162-1.667) and females (d' = 0.55, 95 %CI 0.210-1.299). In females, Aq+ improved TuG by -7.02 % (d' = 0.92, 95 %CI 1.699-0.141) while Glu worsened performance by 4.18 % (P = 0.04). Aq+ reduced analgesia by 71.6 %, compared to Glu (P = 0.02; d' = 0.82, 95 %CI 1.524-0.123). Aq+ was superior to Glu at improving pain, KOOS subscales, physical function and analgesia use in mild-sKOA. Given these data, Aq+ should be considered as a supplementary treatment for early-stage-KOA and may have the potential to reduce use of pain medication, although larger replication studies are required.

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats.

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Ascorbic acid metabolism and polyol pathway in diabetes.

It has been reported previously that the plasma concentration of ascorbic acid (AA) is reduced in streptozocin-induced diabetic rats and can be normalized by treatment with the aldose reductase inhibitor tolrestat. This study was designed to investigate further the relationship between the polyol pathway and AA metabolism in diabetic rats. Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol supplementation was effective in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite low plasma AA concentration, there was increased urinary excretion of AA that was reversed by treatment with either tolrestat or myo-inositol. In contrast, AA supplementation normalized plasma AA concentrations while further increasing urinary AA excretion. The abnormality of AA metabolism was less severe in galactose-fed rats, which had normal plasma AA levels and only minor increases in urinary AA excretion. These studies demonstrated a disturbance in the regulation of plasma and urinary AA concentration in experimental diabetes and confirmed the relationship of AA with the polyol pathway. Because AA has many important biological functions, abnormalities of AA metabolism could be important in the pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this could be another site of action for aldose reductase inhibitors.

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities.

The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.