Does Vit C incr the risk of mortality in women with diabetes

This forum will focus on analyzing recent clinical studies of vitamin C.

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Does Vit C incr the risk of mortality in women with diabetes

Post Number:#1  Post by mstill » Tue Dec 20, 2005 8:01 pm

Does supplemental vitamin C increase cardiovascular disease
risk in women with diabetes?
http://www.ajcn.org/cgi/content/full/80/5/1194

"A 15-year study of postmenopausal women found that diabetic
women who reported taking at least 300 mg/day of vitamin C
from supplements when the study began were at significantly
higher risk of death from coronary heart disease and stroke
than those who did not take vitamin C supplements."

I am very interested in Dr. Fonorow's evaluation of these results.
My wife is a diabetic and is taking 3000 MG of Vitamin C per day.
She is 70 years old and severely under weight, but feisty as teenager.

Thanks for your assistance.

Dave_iis@umich.edu
The Accountant



Disclaimer: The opinions expressed are my own and do not necessarily reflect those of the Vitamin C Foundation or its members. If you are ill, please seek medical attention.

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Study is Not Convincing

Post Number:#2  Post by ofonorow » Wed Dec 21, 2005 11:24 am

My initial reaction is this study's conclusions do not match the design, that it ignores other studies which have shown the opposite, and that it is based upon voluntary questionnaires, and not blood serum level measurements.

They also eliminated almost 1/3 of the participants (over 1000 responders) for what sound like good reasons, but who knows..

Note: The UK study (analysis posted in this forum) that found a large mortality benefit from vitamin C was based on serum levels. (One can argue that in the Harvard Nurses study, also questionanaires, nurses understood the importance of keeping detailed and accurate records.)

The other problem is the hypothesis and design. They begin with the idea that vitamin C is bad for diabetics, and this is what they claim to have found. (Results contrary to what researchers set out to prove are more interesting. For example, if the Linus Pauling Institute’s was doing a study on vitamin C, and their hypothesis was the vitamin C was beneficial for diabetics, yet they found the opposite, this would carry more weight. Readers would know that they tried every bias they could think of, and yet had to admit they are wrong. In this case, we are to believe that their finding, which matches their hypothesis, is unbiased?)

Another problem that one notices immediately is the end-point. Death. It should be life expectancy at the baseline. If all the people age 80 were taking high vitamin C, and all the women age 40 were not, higher deaths would be entirely expected in the vitamin C group!. (I think it is reasonable to assume people as they age tend to supplement more.) This is like saying that 4 degrees Celsius is double 2 degrees. Does 4 degrees feel twice as warm as 2 degrees? Why not? The scale is not normalized to zero. 4 degrees Celciius is really 277 degrees from absolute zero, while 2 degrees is 275 Kelvin.

For the sake of argument, let’s assume that they have discovered something, that higher vitamin C does, in fact, reduce diabetic mortality. This would be a highly surprising result, and if it is a true effect, it is probably not for the reasons they speculate.

Vitamin C and glucose enter many cells through the same insulin mediated transport. If there is high serum blood sugar one can assume that LESS vitamin C makes it into cells, or that the vitamin is blocked from entering cells for the same reasons glucose is blocked - "clogged" membranes.

I'll do more research and post the results of studies that seem better designed.
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Question Moot if you Reverse Diabetes Type 2

Post Number:#3  Post by ofonorow » Wed Dec 21, 2005 1:03 pm

The value of a theory is to make sense out of a maze of conflicting data.

Such may be the value of Thomas Smith’s theory of Diabetes Type 2 (See http://www.healingmatters.com ), especially when one is faced with over 700 MEDLINE studies from the search of "diabetes" and "Vitamin C". (Looking at this mass of research is confusing, and beyond the scope of my expertise or primary interest. However, I may have one advantage. If what medicine thinks causes diabetes, is wrong, and if Smith’s ideas are correct, then maybe we can weed out some reports. )

The question is simple. Should diabetics be taking vitamin C, or shouldn’t they? And how much?
Can science help us answer that simple question?

As background, Smith was able to cure his Type 2 diabetes in 90 days by eliminating man-made processed (trans) fats and supplementing Omega-3 fatty acids. His explanation is that this protocol corrects malfunctioning cellular membranes which otherwise become clogged due to the trans fats, and impurities in these fats. I became interested because of the Ely GAA theory which predicts that diabetic cells would have a doubly hard time obtaining vitamin C.

First an anecdote that Mr. Till may expand on. Several years ago his mother-in-law was in the hospital with very high blood sugar, over 300 mg/dl if memory serves. Insulin was not working. The doctors could not control her blood sugar. This condition is very dangerous, and Till’s wife took matters into her own hands and started giving her mother the Tower HeartTechnology product. About a week later, I received another "frantic call." This time they were worried about hypoglycemia (low blood sugar) in this woman. Her blood sugar had dropped below 80 mg/dl - in the hospital. The doctors said "they didn’t know what was in the product (high vitamin C and lysine) but that she should keep taking it."

We never really understood what happened. It is hard to even speculate. Certainly, what ever it was that was blocking glucose from entering her cells was overcome by the high vitamin C intake. Perhaps insulin was potentated? Perhaps a lucky coincidence from eating hospital food? Or maybe the mechanism was discovered in the 1930s, as described next by Stone?

Now back to the question: Is high vitamin C a good or bad idea for diabetics?

First, Irwin Stones book provides a historical perspective since there was already a mountain of research, according to Stone, in the 1930s.

http://vitamincfoundation.org/stone/chapt23-25.htm
stone wrote:Not long after the discovery of ascorbic acid in the early 1930s, tests on guinea pigs indicated that ascorbic acid had a profound influence on the body's sugar utilization. In 1934, C.G. King and coworkers (1), at the University of Pittsburgh, showed that guinea pigs maintained on low levels of ascorbic acid developed degeneration of the Islets of Langerhands. Guinea pigs depleted of ascorbic acid showed a low glucose tolerance which was rapidly regained on feeding them ascorbic acid. In 1935 and 1937, they also demonstrated that injection of sublethal doses of diphtheria toxin (increased stress) further diminished their tolerance to sugar in proportion to the length of their ascorbic acid deprivation.

These results were confirmed and extended in a comprehensive series of papers from India by Banerjee (2), starting in 1943. He not only confirmed that guinea pigs with scurvy showed poor sugar tolerance, but indicated that the insulin content of the pancreas of scorbutic guinea pigs is reduced to about 1/8 that of normal guinea pigs. He observed gross changes in the microscopic appearance of sections of the pancreas from scorbutic guinea pigs. The appearance returned to normal when the guinea pigs were given ascorbic acid. He also reported that the normal conversion of excess sugar into glycogen reserves for liver storage is also impaired in scurvy. In 1947, using improved laboratory techniques, he confirmed his earlier results and revised his estimate of the insulin content of the pancreas of scorbutic guinea pigs to one-quarter that of normal. He also states in this paper:
The disturbed carbohydrate metabolism as seen in scurvy is due to a deficiency of insulin secretion and a chronic deficiency of this vitamin may be one of the etiological factors (causes) of diabetes mellitus in human subjects.



Read Chapter 23 in Stones book for a defense of the proposition that vitamin C is important for the prevention of Diabetes.

Medline Studies

The following study found lower DNA damage markers in subjects receiving vitamin C. This is a good thing.

Inter-relationships between DNA damage, ascorbic acid and glycaemic control in Type 2 diabetes mellitus.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
abstract wrote:CONCLUSIONS: The novel finding of a significant inverse relationship between plasma AA and DNA damage in Type 2 DM indicates that poorly controlled diabetic subjects might benefit from increased dietary vitamin C. The data also have important implications for biomarker profiling to identify those subjects who might benefit most from intensive therapy. Longer-term follow-up is underway.


The following studies confirm findings that vitamin C is generally lower in diabetics. The next one classifies 800 mg daily a "high dose" and found this level was not sufficient to raise blood ascorbate concentrations.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
High Dose Oral Vitamin C Partially Replenishes Vitamin C Levels in Patients with Type 2 Diabetes and Low Vitamin C Levels but Does Not Improve Endothelial Dysfunction or Insulin Resistance.

abstract wrote:Thirty two diabetic subjects with plasma vitamin C < 40 microM were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C, 800 mg/day for 4 weeks. Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to acetylcholine (ACh), sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 weeks of treatment. In the placebo group (n = 17), plasma vitamin C (22 +/- 3 microM), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 microU/ml), and SIClamp (2.06 +/- 0.29) did not change significantly after placebo treatment. In the vitamin C group (n = 15), basal plasma vitamin C (23 +/- 2 microM) increased to 48 +/- 6 microM (p < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (> 80 microM). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 microU/ml), SIClamp (2.71 +/- 0.46), or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high dose oral vitamin C therapy resulting in incomplete replenishment of vitamin C levels is ineffective at improving endothelial dysfunction and insulin resistance in type 2 diabetes.




Lipid peroxidation and antioxidant status in patients with diabetic retinopathy.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum

abstract wrote:Non Insulin Dependent Diabetes Mellitus is responsible for 60% cases of retinopathy in the population and is one of the common cause of blindness. Oxidative stress as measured by the levels of malondialdehyde, superoxide dismutase (SOD), glutathione peroxidase (GPx) and vitamin C was measured in 50 normal controls, 40 diabetics without complications, 22 diabetics with proliferative and 20 with nonproliferative retinopathy respectively. Our finding suggests that lipid peroxidation increases (P < 0.001) with the increase in severity and duration of diabetes. Antioxidants SOD and vitamin C decrease with the progression of the disease, however GPx tends to increase in the later part of the disease.


http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Ascorbic Acid and Alpha Tocopherol Antioxidant Status of Type 2 Diabetes Mellitus Patients seen in Lagos.

abstract wrote:Summary: This study was carried out with the aim of assessing the plasma status of ascorbic acid and alpha-tocopherol in Nigerian type 2 diabetes mellitus patients It was a cross sectional study, made up of 70 type 2 diabetes mellitus patients and 40 healthy controls. The plasma levels of vitamins C and E were measured, so also were the fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1C). Results showed significantly lower plasma levels of vitamin C and vitamin E in the patients, compared with the controls. The correlation studies between vitamins C and E on the one hand, versus (FPG) and HbA1c on the other hand were not contributory.The conclusion from this study, is that, there is a reduction in plasma levels of anti-oxidant vitamins C and E in type 2 DM but this does not have any particular relationship with the levels of FPG or HbA1C. Keywords: type 2 Dm, ascorbic Acid, alpha tocopherol antioxidant status.


http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
Diabetes mellitus worsens antioxidant status in patients with chronic pancreatitis.

abstract wrote:BACKGROUND: Patients with chronic pancreatitis (CP) are at high risk of antioxidant deficiencies. Furthermore, this disease can lead to diabetes mellitus (DM) that could exacerbate the severity of oxidative stress. Oxidative stress and the resulting LDL oxidation are a major cause of atherosclerosis. OBJECTIVE: The objective of the study was to ascertain whether diabetes significantly modifies oxidative status in patients with CP. DESIGN: CP patients with or without DM were compared with type 1 DM patients and healthy control subjects. RESULTS: Two-way factorial analyses showed that a decrease in the plasma concentrations of vitamin A, vitamin E, and carotenoids accompanied both CP and DM, and CP was also associated with lower plasma concentrations of selenium and zinc, lower catalase activity, and higher plasma concentrations of copper. The lag phase of LDL oxidation was lower in CP patients with or without DM than in the control subjects, whereas there was no significant difference between type 1 DM patients and control subjects. Multivariate analysis showed that LDL vitamin E (R2 = 0.24, P < 0.0001) and fasting plasma glucose (R2 = 0.32, P < 0.0001) concentrations were the main determinants of the lag phase of LDL oxidation. CONCLUSIONS: Antioxidant status is altered in CP patients, particularly in those who also have DM. In these patients, a vitamin E deficiency and an elevated plasma glucose concentration were associated with significantly higher LDL oxidizability.



At this point is should be pointed out that experts in the use of alternative medicine for the treatment of Diabetes rely on up to 600 mg daily of Alpha-Lipoic Acid.

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
Effects of triple antioxidant combination (vitamin E, vitamin C and alpha-lipoic acid) with insulin on lipid and cholesterol levels and fatty acid composition of brain tissue in experimental diabetic and non-diabetic rats

abstract wrote:The aim of this research was to examine the effects of a triple antioxidant combination (vitamins E (VE) and C (VC) plus alpha-lipoic acid (LA)) on the total lipid and cholesterol levels and the fatty acid composition of brain tissues in experimental diabetic and non-diabetic rats. VE and LA were injected intraperitoneally (50 mg/kg) four times per week and VC was provided as a supplement dissolved in the drinking water (50 mg/kg). In addition, rats in the diabetes 1 and D+VELAVC groups were given daily by subcutaneous insulin injections (8 IU/kg), but no insulin was given to rats in the diabetes 2 group. The results indicate that the brain lipid levels in the D+VELAVC, diabetes 1 and diabetes 2 groups were higher than in the control group (P<0.01). Total lipid was also higher in the non-diabetic rats treated with LA and VC. Total cholesterol was higher in the diabetes 1 and diabetes 2 groups (P<0.05) than in controls. Cholesterol levels were similar in the D+VELAVC and LA groups but lower in the VC, VE and VELAVC groups of non-diabetic rats (P<0.05 and P<0.01). In respect of fatty acid composition, palmitic acid levels were lower in the diabetes 2 and non-diabetic VE groups than the control group (P<0.05), but higher in the non-diabetic LA group (P<0.05). Oleic acid (18:1 n-9) levels were lower in the diabetic and non-diabetic groups than the control group (P<0.01), but higher in the non-diabetic LA group. Arachidonic acid (20:4 n-6) levels were similar in the diabetes 1, D+VELAVC and control groups (P>0.05) but higher in the non-diabetic VE, VC, LA and VEVCLA groups (P<0.05) and lower in the diabetes 2 group (P<0.05). Docosahexaenoic acid (22:6 n-3) was elevated in the diabetes 2 and VEVCLA groups (P<0.01, P<0.05). In conclusion, the current study confirmed that treatment with a triple combination of VE, VC and LA protects the arachidonic acid level in the brains of diabetic and non-diabetic rats.


Note, rats make their own vitamin C.


http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
The role of antioxidant micronutrients in the prevention of diabetic complications.
abstract wrote:Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.


http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
The impact of vitamins and/or mineral supplementation on blood pressure in type 2 diabetes.

abstract wrote:The present study designed to assess the effect of Mg+Zn, vitamin C+E, and combination of these micronutrients on blood pressure in type 2 diabetic patients.

RESULTS: Results indicate that after three months of supplementation levels of systolic, diastolic and mean blood pressure decreased significantly in the MV group by 8 mmHg (122 +/- 16 vs. 130 +/- 19 mmHg), 6 mmHg (77 +/- 9 vs. 83 +/- 11 mmHg), and 7 mmHg (92 +/- 9 vs. 99 +/- 13 mmHg), respectively (p < 0.05). Also combination of vitamin and mineral supplementation had significantly effects in increasing serum potassium (p < 0.05) and in decreasing serum malondialdehyde (p < 0.05). There was no significant change in the levels of these parameters in the other three groups. CONCLUSION: The results of the present study indicated that in type 2 diabetic patients a combination of vitamins and minerals, rather than vitamin C and E or Mg and Zn alone, might decrease blood pressure.


The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
abstract wrote:OBJECTIVE: The purpose of the present study was to assess the impact of Mg + Zn, Vitamins C + E, and combination of these micronutrients on serum lipid and lipoprotein profiles in type 2 diabetic patients.

RESULTS: Results indicate that after 3 months of supplementation mean serum levels of HDL-c and apo A1 increased significantly in the MV group by 24% (50.4 +/-19.3 mg/dl versus 40.6 +/- 10.8 mg/dl) and 8.8% (169.8 +/- 33.8 mg/dl versus 156.1+ /- 23.9 mg/dl), respectively (P < 0.01). There were no significant changes in the levels of these parameters in the other three groups. Serum levels of total cholesterol, LDL-c, triglyceride, and apo B were not altered after supplementation in all four groups. CONCLUSION: It is concluded that since co-supplementation of Mg, Zn, Vitamins C and E significantly increases HDL-c and apo A1, supplementation of these micronutrients could be recommended for the type 2 diabetic patients based on their daily requirements.



Bottom Line


There is scientific support for the proposition that diabetics require higher vitamin C.

I personally don’t believe the finding in the study that started this discussion, but the point may be moot. If one can totally reverse ones Type 2 Diabetes, by following the Thomas Smith protocol for 90 days, then there is no issue taking large supplemental dosages of vitamin C. In any event consider R-Alpha Lipoic Acid up to 600 mg daily
Owen R. Fonorow
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Vitamin E and diabetes

Post Number:#4  Post by Dolev » Wed Dec 21, 2005 5:42 pm

Although this is a vitamin C forum, the concerned readers should know of the benefits of vit E in diabetes. Evan Shute wrote that by increasing peripheral circulation, vitamin E has prevented the amputation of "many a foot". The same vit E quality can save many an eye, as the following really cool study proves:

abstract wrote:O B J E C T I V E— To determine the effectiveness of vitamin E treatment in normalizing re t i n a l blood flow and renal function in patients with ,10 years of type 1 diabetes.

RESEARCH DESIGN AND METHODS— A n 8-month randomized double-masked p l a c e b o - c o n t rolled crossover trial evaluated 36 type 1 diabetic and 9 nondiabetic subjects. Subjects were randomly assigned to either 1,800 IU vitamin E/day or placebo for 4 months and followed, after treatment cro s s o v e r, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized cre a t i n i n e clearance from timed urine collections.

R E S U LT S— After vitamin E treatment, serum levels of vitamin E were significantly elevated (P , 0.01) in both type 1 diabetic and control patients. Hemoglobin A1 c was not affected by vitamin E treatment. Diabetic patient baseline retinal blood flow (29.1 ± 7.5 pixel2/s) was s i g n i ficantly (P = 0.030) decreased compared with that of nondiabetic subjects (35.2 ± 7.2 p i x e l2/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5 ± 7.8 pixel2/s) was s i g n i ficantly increased (P , 0.001) and was comparable with that of nondiabetic subjects.A d d i t i o n a l l y, vitamin E treatment significantly (P = 0.039) normalized elevated baseline creatinine clearance in diabetic patients.

C O N C L U S I O N S— Oral vitamin E treatment appears to be effective in normalizing re t i n a l hemodynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephro p a t h y.Diabetes Care 22:1245–1251, 1999
Dolev


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