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Home | Low Carb diet to treat type-2 diabetes | THE CAUSES: Fructose, insulin resistance, ascorbate, and collagen | More Jounral articles on COLLAGEN and its role in diabetic pathologies | Ascorbic acid diabetes studies | Journal articles on polyol pathway and ascorbate | Ascorbate role and not hyperglycemia is pathogenic | Explanatory letter recommending ascorbate supplement

Ascorbic acid diabetes studies

What the collection of pasted articles show

The diabetic has low level of ascorbate which is a powerful water soluble antioxidant.  Ascorbate reduction promotes increase oxidative damage. Most conspicuous is that of Milliard reaction of glucose.  It is not the high glucose, but the failure of the ascorbate which besides being an antioxidant is involved as a co-enzyme in 7 different reactions.  Of particular importance is its role in the production of collagen.  Collagen is the most important family of proteins, and the failure to have sufficient ascorbate results in a pro-pathological rate of the product of defective collagen.  The fix is to take at least one gram of ascorbate.  The journal articles selected for publication here were chosen on the basis of relevance.  The sum total of these articles support already existing strong evidence that tight management of glucose through drugs that increase insulin or insulin sensitivity is not in the diabetics interest, but in pharma’s.  A second point implied is that a very low carbohydrate diet will reduce the harm of increased insulin. 

Type 2 diabetics (T2D) are insulin resistant, they have too much insulin, and thus increasing it further with drugs only increases the side effects, which are of course blamed on sugar rather than the drugs.   

Diabetes Research and Clinical Practice Volume 9, Issue 3, 1990, Pages 239-244

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. [Human’s, unlike rats, don’t synthesize ascorbic acid, thus making diabetic rats a poor model for extrapolation to humans.  Most mammals 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.


Diabetologia 1991 34: 171-175

Disturbed handling of ascorbic acid in diabetic patients with and without

Micro-angiopathy during high dose ascorbate supplementation


Summary. Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a co­ factor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic  acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched  diabetic  patients with and without microangiopathy (small vessel bleeding) and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had  lower ascorbic acid concentrations  than  those without   microangiopathy and control subjects (42.1 ± 19.3 vs 55.6 ± 20.0, p < 0.01, vs 82.9 ± 30.9 )lmol/1, p < 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 ± 0.46 vs 0.61 ± 0.26,  p < 0.01, vs 0.38 ± 0.14,  p < 0.001).  At three weeks, ascorbate concentrations  rose in all groups (p < 0.0001) and was maintained in control subjects (151.5 ± 56.3 ) lmol/1), but fell in both diabetic groups by six weeks (p < 0.01).  Dehydroascorbate/ascorbate  ratios  fell  in  all groups at  three  weeks (p < 0.0001) but  rose again in the diabetic groups by six weeks (p < 0.001) and was unchanged in the control  subjects. Dehydroascorbate  concentrations rose significantly from baseline in all groups by six weeks of ascorbic  acid  supplementation   (p < 0.05).  No  significant changes were observed  in fructosamine concentrations  in any group during the study. Diabetes mellitus is associated with a major disturbance of ascorbic acid metabolism which is only partially corrected by ascorbate supplementation.

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^   Diabetes 1988 Mar; 37(3): 359-361.

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.



Diabetic angiopathy is a form of angiopathy associated with diabetes mellitus. While not exclusive, the two most common forms are Diabetic retinopathy and Diabetic nephropathy, whose pathophysiologies are largely identical.


As typical of pharma in framing the discussion of a topic, it has blamed it in high sugar rather than low ascorbate.  As insulin is required for glucose uptake, hyperglycemia in diabetes mellitus does not result in a net increase in intracellular glucose in most cells. However, chronic dysregulated blood glucose in diabetes is toxic to cells of the vascular endothelium which passively assimilate glucose.

The putative toxicity of glucose is not established.  For example tight management of glucose in diabetics is strongly associated with a worse outcome, heart attacks and death.  One such trial was using rosiglitazone, Prof. Ben Goldacre, Bad Pharma p 91-93.


^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^  Diabetes 1989 Feb; 38(2): 257-261.

Ascorbic Acid Metabolism and Polyol Pathway in Diabetes


It has been reported previously that the plasma concentration of ascorbic acid (AA) is reducedin 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 myoinositol. 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 [milk sugar--lactose is glucose + galactose], 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.

An Investigation of the Relationship between Free Radical Activity and Vitamin C Metabolism in Elderly Diabetic Subjects with Retinopathy



Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.


This misses the main problem, that plasma ascorbate reflects recent diet, while leucocytes is a measurement of storage.  See testing for levels in

DiabeticMedicine, Nov. 1994

Low Plasma Ascorbate Levels in Patients with Type 2 Diabetes Mellitus Consuming Adequate Dietary Vitamin C


Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 ± 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 ± 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 ± 28.3 (patients) vs 69.5 ± 33.4 (controls) mg; questionnaire, 54.0 ± 28.9 (patients) vs 65.0 ± 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 ± 19.1 μol l−1) and dehydroascorbate (27.6 ± 6.4 μmol l−1) levels were significantly lower in patients vs in controls (68.8 ± 36.0 and 31.8 ± 4.8 μmol l−1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake. Vitamin C supplementation of the diabetic diet deserves further consideration.


The Chinese diet is low in fruit, thus vitamin C, therefore they should be an ideal group to benefit from a supplement.   Again and again I see a promising therapy is for a non-patentable drug or supplement it is ignored in the US but not in China.  And if it is reluctantly becomes used, often it is in too low a dose, or an ineffective analogue.  Below is another example of profits before patients in the US.  This article, though in English has 7 Chinese authors, and is published in 2016.

Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators

  • PLOS Published: September 29, 2016



Despite growing interest in the protective role that dietary antioxidant vitamins may have in the development of type 2 diabetes (T2D), little epidemiological evidence is available in non-Western populations especially about the possible mediators underlying in this role. The present study aimed to investigate the association of vitamin C and vitamin E intakes with T2D risk in Chinese adults and examine the potential mediators. 178 incident T2D cases among 3483 participants in the Harbin People Health Study (HPHS), and 522 newly diagnosed T2D among 7595 participants in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases (HDNNCDS) were studied. In the multivariable-adjusted logistics regression model, the relative risks (RRs) were 1.00, 0.75, and 0.76 (Ptrend = 0.003) across tertiles of vitamin C intake in the HDNNCDS, and this association was validated in the HPHS with RRs of 1.00, 0.47, and 0.46 (Ptrend = 0.002). The RRs were 1.00, 0.72, and 0.76 (Ptrend = 0.039) when T2D diagnosed by haemoglobin A1c in the HDNNCDS. The mediation analysis discovered that insulin resistance (indicated by homeostasis model assessment) and oxidative stress (indicated by plasma total antioxidative capacity) partly mediated this association. But no association was evident between vitamin E intake and T2D. In conclusion, our research adds further support to the role of vitamin C intake in reducing the development of T2D in the broader population studied. The results also suggested that this association was partly mediated by inhibiting or ameliorating oxidative stress and insulin r

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Harvard Prof. Marcia Angell, MD., former Chief Editor of NEJM wrote: “We certainly are in a health care crisis, ... If we had set out to design the worst system that we could imagine, we couldn't have imagined one as bad as we have.”


The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment